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Drug-microbiota interactions: an emerging priority for precision medicine

Drug-microbiota interactions: an emerging priority for precision medicine

  • Spear, B. B., Heath-Chiozzi, M. & Huff, J. Clinical application of pharmacogenetics. Trends Mol. Med. 7, 201–204 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lazarou, J., Pomeranz, B. H. & Corey, P. N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279, 1200–1205 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pirmohamed, M. et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 329, 15–19 (2004).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Feitosa Ramos, S. et al. Adverse drug reactions to anti-infectives in hospitalized children: a multicenter study in Brazil. J. Pediatr. Infect. Dis. Soc. 12, 76–82 (2023).

    Article 

    Google Scholar
     

  • Jiang, H. et al. Adverse drug reactions and correlations with drug-drug interactions: a retrospective study of reports from 2011 to 2020. Front. Pharm. 13, 923939 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Zhang, Y. et al. Emergency hospitalizations for adverse drug events in China: clinical pharmacists’ approach to assessment and categorization. Pharmacoepidemiol. Drug Saf. 30, 636–643 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Konig, I. R., Fuchs, O., Hansen, G., von Mutius, E. & Kopp, M. V. What is precision medicine? Eur. Respir. J. 50, 1700391 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Ramaswami, R., Bayer, R. & Galea, S. Precision medicine from a public health perspective. Annu. Rev. Public Health 39, 153–168 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Prasad, R. B. & Groop, L. Precision medicine in type 2 diabetes. J. Intern. Med. 285, 40–48 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Buitelaar, J. et al. Toward precision medicine in ADHD. Front. Behav. Neurosci. 16, 900981 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ahmed, S., Zhou, Z., Zhou, J. & Chen, S. Q. Pharmacogenomics of drug metabolizing enzymes and transporters: relevance to precision medicine. Genom. Proteom. Bioinforma. 14, 298–313 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Clarke, J. D. & Cherrington, N. J. Nonalcoholic steatohepatitis in precision medicine: unraveling the factors that contribute to individual variability. Pharm. Ther. 151, 99–106 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Zhou, Y., Tremmel, R., Schaeffeler, E., Schwab, M. & Lauschke, V. M. Challenges and opportunities associated with rare-variant pharmacogenomics. Trends Pharm. Sci. 43, 852–865 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chang, W. C., Tanoshima, R., Ross, C. J. D. & Carleton, B. C. Challenges and opportunities in implementing pharmacogenetic testing in clinical settings. Annu. Rev. Pharm. Toxicol. 61, 65–84 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Johnson, J. A. & Cavallari, L. H. Pharmacogenetics and cardiovascular disease-implications for personalized medicine. Pharm. Rev. 65, 987–1009 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Limdi, N. A. et al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood 115, 3827–3834 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davies, S. M. et al. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Blood 111, 2984–2990 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roses, A. D. Pharmacogenetics in drug discovery and development: a translational perspective. Nat. Rev. Drug Discov. 7, 807–817 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Swen, J. J. et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet 401, 347–356 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Haidar, C. E., Crews, K. R., Hoffman, J. M., Relling, M. V. & Caudle, K. E. Advancing pharmacogenomics from single-gene to preemptive testing. Annu Rev. Genom. Hum. Genet 23, 449–473 (2022).

    Article 

    Google Scholar
     

  • Lavertu, A. et al. Pharmacogenomics and big genomic data: from lab to clinic and back again. Hum. Mol. Genet 27, R72–R78 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weinshilboum, R. M. & Wang, L. Pharmacogenomics: precision medicine and drug response. Mayo Clin. Proc. 92, 1711–1722 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Roden, D. M. et al. Pharmacogenomics: challenges and opportunities. Ann. Intern. Med. 145, 749–757 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Eichelbaum, M., Ingelman-Sundberg, M. & Evans, W. E. Pharmacogenomics and individualized drug therapy. Annu. Rev. Med. 57, 119–137 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Evans, W. E. & Johnson, J. A. Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu Rev. Genom. Hum. Genet 2, 9–39 (2001).

    Article 
    CAS 

    Google Scholar
     

  • Pirmohamed, M. Pharmacogenomics: current status and future perspectives. Nat. Rev. Genet 24, 350–362 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kalow, W., Tang, B. K. & Endrenyi, L. Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics 8, 283–289 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lindell, A. E., Zimmermann-Kogadeeva, M. & Patil, K. R. Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota. Nat. Rev. Microbiol. 20, 431–443 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nie, P. et al. Gut microbiome interventions in human health and diseases. Med. Res. Rev. 39, 2286–2313 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Hou, K. et al. Microbiota in health and diseases. Signal Transduct. Target Ther. 7, 135 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Steiner, H. E. et al. Role of the gut microbiome in cardiovascular drug response: the potential for clinical application. Pharmacotherapy 42, 165–176 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Zhou, C. B., Zhou, Y. L. & Fang, J. Y. Gut microbiota in cancer immune response and immunotherapy. Trends Cancer 7, 647–660 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Roviello, G., Iannone, L. F., Bersanelli, M., Mini, E. & Catalano, M. The gut microbiome and efficacy of cancer immunotherapy. Pharm. Ther. 231, 107973 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Lee, K. A. et al. Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma. Nat. Med. 28, 535–544 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scepanovic, P. et al. A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals. Microbiome 7, 130 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, P. et al. Gut microbial signatures can discriminate unipolar from bipolar depression. Adv. Sci. (Weinh.) 7, 1902862 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • Vinje, S., Stroes, E., Nieuwdorp, M. & Hazen, S. L. The gut microbiome as novel cardio-metabolic target: the time has come! Eur. Heart J. 35, 883–887 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Wei, M. Y. et al. The microbiota and microbiome in pancreatic cancer: more influential than expected. Mol. Cancer 18, 97 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Robertson, R. C. et al. Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota. Microbiome 6, 95 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570, 462–467 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Penalver Bernabe, B., Cralle, L. & Gilbert, J. A. Systems biology of the human microbiome. Curr. Opin. Biotechnol. 51, 146–153 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Enright, E. F., Gahan, C. G., Joyce, S. A. & Griffin, B. T. The impact of the gut microbiota on drug metabolism and clinical outcome. Yale J. Biol. Med. 89, 375–382 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kinross, J. M., Darzi, A. W. & Nicholson, J. K. Gut microbiome-host interactions in health and disease. Genome Med. 3, 14 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rodriguez, J. M. et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Micro. Ecol. Health Dis. 26, 26050 (2015).


    Google Scholar
     

  • Piazzon, M. C. et al. Under control: how a dietary additive can restore the gut microbiome and proteomic profile, and improve disease resilience in a marine teleostean fish fed vegetable diets. Microbiome 5, 164 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shkoporov, A. N. et al. Reproducible protocols for metagenomic analysis of human faecal phageomes. Microbiome 6, 68 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Montassier, E. et al. CLOUD: a non-parametric detection test for microbiome outliers. Microbiome 6, 137 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, L. et al. Analysis of microbiota in elderly patients with Acute Cerebral Infarction. PeerJ 7, e6928 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jiang, H. et al. Impact of host intraspecies genetic variation, diet, and age on bacterial and fungal intestinal microbiota in tigers. Microbiologyopen 9, e1050 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Visconti, A. et al. Interplay between the human gut microbiome and host metabolism. Nat. Commun. 10, 4505 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chua, L. L. et al. Reduced microbial diversity in adult survivors of childhood acute lymphoblastic leukemia and microbial associations with increased immune activation. Microbiome 5, 35 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jackson, M. A. et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat. Commun. 9, 2655 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heirali, A. A. et al. The effects of inhaled aztreonam on the cystic fibrosis lung microbiome. Microbiome 5, 51 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Javdan, B. et al. Personalized mapping of drug metabolism by the human gut microbiome. Cell 181, 1661–1679.e22 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weersma, R. K., Zhernakova, A. & Fu, J. Interaction between drugs and the gut microbiome. Gut 69, 1510–1519 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Alexander, J. L. et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat. Rev. Gastroenterol. Hepatol. 14, 356–365 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Saad, R., Rizkallah, M. R. & Aziz, R. K. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes. Gut Pathog. 4, 16 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scher, J. U., Nayak, R. R., Ubeda, C., Turnbaugh, P. J. & Abramson, S. B. Pharmacomicrobiomics in inflammatory arthritis: gut microbiome as modulator of therapeutic response. Nat. Rev. Rheumatol. 16, 282–292 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Ting, N. L., Lau, H. C. & Yu, J. Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes. Gut 71, 1412–1425 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Panebianco, C., Andriulli, A. & Pazienza, V. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies. Microbiome 6, 92 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Doestzada, M. et al. Pharmacomicrobiomics: a novel route towards personalized medicine? Protein Cell 9, 432–445 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hassan, R. et al. Drug response in association with pharmacogenomics and pharmacomicrobiomics: towards a better personalized medicine. Brief. Bioinform 22, bbaa292 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Sharma, A., Buschmann, M. M. & Gilbert, J. A. Pharmacomicrobiomics: the holy grail to variability in drug response? Clin. Pharm. Ther. 106, 317–328 (2019).

    Article 

    Google Scholar
     

  • Tsunoda, S. M., Gonzales, C., Jarmusch, A. K., Momper, J. D. & Ma, J. D. Contribution of the gut microbiome to drug disposition, pharmacokinetic and pharmacodynamic variability. Clin. Pharmacokinet. 60, 971–984 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, H. L. et al. Targeted approaches for in situ gut microbiome manipulation. Genes (Basel) 9, 351 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Wong, W. F. & Santiago, M. Microbial approaches for targeting antibiotic-resistant bacteria. Micro. Biotechnol. 10, 1047–1053 (2017).

    Article 

    Google Scholar
     

  • El Rouby, N., Lima, J. J. & Johnson, J. A. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin. Drug Metab. Toxicol. 14, 447–460 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hauser, A. S. et al. Pharmacogenomics of GPCR drug targets. Cell 172, 41–54 e19 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chaudhry, S. R. et al. Pharmacogenetic prediction of individual variability in drug response based on CYP2D6, CYP2C9 and CYP2C19 genetic polymorphisms. Curr. Drug Metab. 15, 711–718 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Muszkat, M. Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9. Clin. Pharm. Ther. 82, 215–218 (2007).

    Article 
    CAS 

    Google Scholar
     

  • Kamath, A. et al. Role of drug transporters in elucidating inter-individual variability in pediatric chemotherapy-related toxicities and response. Pharmaceuticals 15, 990 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Joharatnam-Hogan, N., Shiu, K. K. & Khan, K. Challenges in the treatment of gastric cancer in the older patient. Cancer Treat. Rev. 85, 101980 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Murgo, A. J. & Espinoza-Delgado, I. Development of novel anticancer agents in older patients: pharmacokinetic, pharmacodynamic, and other considerations. Cancer J. 11, 481–487 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schwartz, J. B. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin. Pharm. Ther. 82, 87–96 (2007).

    Article 
    CAS 

    Google Scholar
     

  • Deneer, V. H. & van Hemel, N. M. Is antiarrhythmic treatment in the elderly different? a review of the specific changes. Drugs Aging 28, 617–633 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Besir, F. H. et al. Enoxaparin-associated giant retroperitoneal hematoma in pulmonary embolism treatment. N. Am. J. Med. Sci. 3, 524–526 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spirk, D. et al. Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER). Eur. Heart J. 33, 921–926 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Saltalamacchia, G., Frascaroli, M., Bernardo, A. & Quaquarini, E. Renal and cardiovascular toxicities by new systemic treatments for prostate cancer. Cancers (Basel) 12, 1750 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Masnoon, N., Shakib, S., Kalisch-Ellett, L. & Caughey, G. E. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 17, 230 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scherholz, M. L., Rao, R. T. & Androulakis, I. P. Modeling inter-sex and inter-individual variability in response to chronopharmacological administration of synthetic glucocorticoids. Chronobiol. Int. 37, 281–296 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Conforti, F. et al. Sex-based differences in response to anti-PD-1 or PD-L1 treatment in patients with non-small-cell lung cancer expressing high PD-L1 levels. A systematic review and meta-analysis of randomized clinical trials. ESMO Open 6, 100251 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Federman, D. D. The biology of human sex differences. N. Engl. J. Med. 354, 1507–1514 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Soldin, O. P. & Mattison, D. R. Sex differences in pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet. 48, 143–157 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scandlyn, M. J., Stuart, E. C. & Rosengren, R. J. Sex-specific differences in CYP450 isoforms in humans. Expert Opin. Drug Metab. Toxicol. 4, 413–424 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rodenburg, E. M., Stricker, B. H. & Visser, L. E. Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands. Br. J. Clin. Pharm. 71, 95–104 (2011).

    Article 

    Google Scholar
     

  • Calcagno, A. et al. Tenofovir plasma concentrations according to companion drugs: a cross-sectional study of HIV-positive patients with normal renal function. Antimicrob. Agents Chemother. 57, 1840–1843 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cerrato, E. et al. Cardiovascular disease in HIV patients: from bench to bedside and backwards. Open Heart 2, e000174 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anderson, G. D. Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J. Women’s Health (Larchmt.) 14, 19–29 (2005).

    Article 

    Google Scholar
     

  • Anderson, G. D. Gender differences in pharmacological response. Int. Rev. Neurobiol. 83, 1–10 (2008).

    Article 
    PubMed 

    Google Scholar
     

  • Siguret, V., Pautas, E. & Gouin-Thibault, I. Warfarin therapy: influence of pharmacogenetic and environmental factors on the anticoagulant response to warfarin. Vitam. Horm. 78, 247–264 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hirsh, J. et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 119, 8S–21S (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cavallari, L. H. & Limdi, N. A. Warfarin pharmacogenomics. Curr. Opin. Mol. Ther. 11, 243–251 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • Park, J. N., Lee, J. S., Noh, M. Y. & Sung, M. K. Association between usual vitamin K intake and anticoagulation in patients under warfarin therapy. Clin. Nutr. Res. 4, 235–241 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guaraldi, G. et al. Efficacy and safety of atazanavir in patients with end-stage liver disease. Infection 37, 250–255 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Greenblatt, D. J., Shader, R. I. & Lofgren, S. Rational psycho-pharmacology for patients with medical diseases. Annu Rev. Med. 27, 407–420 (1976).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lv, C., Lv, J., Liu, Y., Liu, Q. & Zou, D. Pediatric pharmaceutical care with anti-infective medication in a patient with acute hematogenous osteomyelitis caused by methicillin-resistant Staphylococcus aureus. Int J. Immunopathol. Pharm. 34, 2058738420925713 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Waldinger, R., Weinberg, G. & Gitman, M. Local anesthetic toxicity in the geriatric population. Drugs Aging 37, 1–9 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Rosmarin, D. M., Lebwohl, M., Elewski, B. E. & Gottlieb, A. B., National Psoriasis, F. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference. J. Am. Acad. Dermatol. 62, 838–853 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • Lewis, J. H. & Stine, J. G. Review article: prescribing medications in patients with cirrhosis – a practical guide. Aliment Pharm. Ther. 37, 1132–1156 (2013).

    Article 
    CAS 

    Google Scholar
     

  • Verbeeck, R. K. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur. J. Clin. Pharm. 64, 1147–1161 (2008).

    Article 
    CAS 

    Google Scholar
     

  • Macpherson, A. J., Heikenwalder, M. & Ganal-Vonarburg, S. C. The liver at the nexus of host-microbial interactions. Cell Host Microbe 20, 561–571 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mani, R. & Pollard, J. R. Antiepileptic drugs and other medications: what interactions may arise? Curr. Treat. Options Neurol. 11, 253–261 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Huang, L., Lizak, P., Dvorak, C. C., Aweeka, F. & Long-Boyle, J. Simultaneous determination of fludarabine and clofarabine in human plasma by LC-MS/MS. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 960, 194–199 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Relling, M. V. et al. Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia. Lancet 356, 285–290 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab. Rev. 34, 83–448 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • O’Malley, M., Healy, P., Daignault, S. & Ramnath, N. Cigarette smoking and gemcitabine-induced neutropenia in advanced solid tumors. Oncology 85, 216–222 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Hamilton, M. et al. Effects of smoking on the pharmacokinetics of erlotinib. Clin. Cancer Res. 12, 2166–2171 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hughes, A. N. et al. Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers. J. Clin. Oncol. 27, 1220–1226 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van der Bol, J. M. et al. Cigarette smoking and irinotecan treatment: pharmacokinetic interaction and effects on neutropenia. J. Clin. Oncol. 25, 2719–2726 (2007).

    Article 
    PubMed 

    Google Scholar
     

  • Kanai, M. et al. A history of smoking is inversely correlated with the incidence of gemcitabine-induced neutropenia. Ann. Oncol. 20, 1397–1401 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dikeocha, I. J., Al-Kabsi, A. M., Miftahussurur, M. & Alshawsh, M. A. Pharmacomicrobiomics: Influence of gut microbiota on drug and xenobiotic metabolism. FASEB J. 36, e22350 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Enright, E. F., Griffin, B. T., Gahan, C. G. M. & Joyce, S. A. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism. Pharm. Res. 133, 170–186 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Vich Vila, A. et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat. Commun. 11, 362 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Garrod, A. E. The incidence of alkaptonuria: a study in chemical individuality. 1902 [classical article]. Yale J. Biol. Med. 75, 221–231 (2002).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Perlman, R. L. & Govindaraju, D. R. Archibald E. Garrod: the father of precision medicine. Genet Med. 18, 1088–1089 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Evans, W. E. & Relling, M. V. Moving towards individualized medicine with pharmacogenomics. Nature 429, 464–468 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Evans, W. E. & McLeod, H. L. Pharmacogenomics-drug disposition, drug targets, and side effects. N. Engl. J. Med. 348, 538–549 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Weinshilboum, R. Inheritance and drug response. N. Engl. J. Med. 348, 529–537 (2003).

    Article 
    PubMed 

    Google Scholar
     

  • Dawed, A. Y. et al. Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials. Lancet Diabetes Endocrinol. 11, 33–41 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beutler, E. Drug-induced hemolytic anemia. Pharm. Rev. 21, 73–103 (1969).

    CAS 
    PubMed 

    Google Scholar
     

  • Beutler, E. The hemolytic effect of primaquine and related compounds: a review. Blood 14, 103–139 (1959).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beutler, E., Dern, R. J. & Alving, A. S. The hemolytic effect of primaquine. III. A study of primaquine-sensitive erythrocytes. J. Lab Clin. Med. 44, 177–184 (1954).

    CAS 
    PubMed 

    Google Scholar
     

  • Vogel, F. Moderne probleme der humangenetik. Ergebn. Inn. Med. Kinderheilk 12, 52–125 (1959).


    Google Scholar
     

  • Xu, H. et al. Multiplexed SNP genotyping using the Qbead system: a quantum dot-encoded microsphere-based assay. Nucleic Acids Res. 31, e43 (2003).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gibbs, R. A. The Human Genome Project changed everything. Nat. Rev. Genet 21, 575–576 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nebert, D. W., Zhang, G. & Vesell, E. S. From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. Drug Metab. Rev. 40, 187–224 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ruiz, C., Zitnik, M. & Leskovec, J. Identification of disease treatment mechanisms through the multiscale interactome. Nat. Commun. 12, 1796 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ming, X. & Laing, B. Bioconjugates for targeted delivery of therapeutic oligonucleotides. Adv. Drug Deliv. Rev. 87, 81–89 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Higgins, G. A., Williams, A. M., Ade, A. S., Alam, H. B. & Athey, B. D. Druggable transcriptional networks in the human neurogenic epigenome. Pharm. Rev. 71, 520–538 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Varga, J., Dobson, L., Remenyi, I. & Tusnady, G. E. TSTMP: target selection for structural genomics of human transmembrane proteins. Nucleic Acids Res. 45, D325–D330 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Somogyi, A. A. & Phillips, E. Genomic testing as a tool to optimise drug therapy. Aust. Prescr. 40, 101–104 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tam, H. K. et al. Allosteric drug transport mechanism of multidrug transporter AcrB. Nat. Commun. 12, 3889 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van de Ven, R. et al. A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration. Blood 112, 2353–2359 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Oslin, D. W. et al. Effect of pharmacogenomic testing for drug-gene interactions on medication selection and remission of symptoms in major depressive disorder: the PRIME care randomized clinical trial. JAMA 328, 151–161 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tardif, J. C. et al. Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial. Eur. Heart J. 43, 3947–3956 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tsutsumi, K. et al. Structures of the wild-type MexAB-OprM tripartite pump reveal its complex formation and drug efflux mechanism. Nat. Commun. 10, 1520 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nigam, S. K. What do drug transporters really do? Nat. Rev. Drug Discov. 14, 29–44 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Surendiran, A., Pradhan, S. C. & Adithan, C. Role of pharmacogenomics in drug discovery and development. Indian J. Pharm. 40, 137–143 (2008).

    Article 
    CAS 

    Google Scholar
     

  • Clayton, T. A., Baker, D., Lindon, J. C., Everett, J. R. & Nicholson, J. K. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc. Natl Acad. Sci. USA 106, 14728–14733 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, H. H., Koshakji, R. P., Silberstein, D. J., Wilkinson, G. R. & Wood, A. J. Racial differences in drug response. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites. N. Engl. J. Med. 320, 565–570 (1989).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yasuda, S. U., Zhang, L. & Huang, S. M. The role of ethnicity in variability in response to drugs: focus on clinical pharmacology studies. Clin. Pharm. Ther. 84, 417–423 (2008).

    Article 
    CAS 

    Google Scholar
     

  • Man, M. et al. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. J. Clin. Pharm. 50, 929–940 (2010).

    Article 
    CAS 

    Google Scholar
     

  • Scharfe, C. P. I., Tremmel, R., Schwab, M., Kohlbacher, O. & Marks, D. S. Genetic variation in human drug-related genes. Genome Med. 9, 117 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bernard, E. et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat. Med. 26, 1549–1556 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Taylor, C. A. et al. IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma. Nat. Med. 28, 2592–2600 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Funnell, T. et al. Single-cell genomic variation induced by mutational processes in cancer. Nature 612, 106–115 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Martinez-Ruiz, C. et al. Genomic-transcriptomic evolution in lung cancer and metastasis. Nature 616, 543–552 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Naranbhai, V. et al. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol. 23, 172–184 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, C. W., Preclaro, I. A. C., Lin, W. H. & Chung, W. H. An updated review of genetic associations with severe adverse drug reactions: translation and implementation of pharmacogenomic testing in clinical practice. Front. Pharm. 13, 886377 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Khan, D. A., Knowles, S. R. & Shear, N. H. Sulfonamide hypersensitivity: fact and fiction. J. Allergy Clin. Immunol. Pract. 7, 2116–2123 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chow, T. G. & Khan, D. A. Sulfonamide hypersensitivity. Clin. Rev. Allergy Immunol. 62, 400–412 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Neuman, M. G. et al. Immunopathogenesis of hypersensitivity syndrome reactions to sulfonamides. Transl. Res. 149, 243–253 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Relman, D. A. & Falkow, S. The meaning and impact of the human genome sequence for microbiology. Trends Microbiol. 9, 206–208 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maringanti, V. S., Bucci, V. & Gerber, G. K. MDITRE: scalable and interpretable machine learning for predicting host status from temporal microbiome dynamics. mSystems 7, e0013222 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Pflughoeft, K. J. & Versalovic, J. Human microbiome in health and disease. Annu. Rev. Pathol. 7, 99–122 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Geurtsen, J. et al. Expression of the lipopolysaccharide-modifying enzymes PagP and PagL modulates the endotoxic activity of Bordetella pertussis. Infect. Immun. 74, 5574–5585 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • ElRakaiby, M. et al. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics. OMICS 18, 402–414 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gutierrez Lopez, D. E., Lashinger, L. M., Weinstock, G. M. & Bray, M. S. Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet. Cell Metab. 33, 873–887 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zheng, P. et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol. Psychiatry 21, 786–796 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xue, M. Y., Sun, H. Z., Wu, X. H., Liu, J. X. & Guan, L. L. Multi-omics reveals that the rumen microbiome and its metabolome together with the host metabolome contribute to individualized dairy cow performance. Microbiome 8, 64 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wilson, I. D. & Nicholson, J. K. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl. Res. 179, 204–222 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Koppel, N., Maini Rekdal, V. & Balskus, E. P. Chemical transformation of xenobiotics by the human gut microbiota. Science 356, eaag2770 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Khalsa, J., Duffy, L. C., Riscuta, G., Starke-Reed, P. & Hubbard, V. S. Omics for understanding the gut-liver-microbiome axis and precision medicine. Clin. Pharm. Drug Dev. 6, 176–185 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Zhao, L. et al. Targeting the human genome-microbiome axis for drug discovery: inspirations from global systems biology and traditional Chinese medicine. J. Proteome Res. 11, 3509–3519 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yachida, S. et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat. Med. 25, 968–976 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Almeida, A. et al. A new genomic blueprint of the human gut microbiota. Nature 568, 499–504 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet 54, 134–142 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Q. et al. Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner. Pharm. Res. 170, 105694 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Kaddurah-Daouk, R. & Weinshilboum, R. Pharmacometabolomics Research Network Metabolomic signatures for drug response phenotypes: pharmacometabolomics enables precision medicine. Clin. Pharm. Ther. 98, 71–75 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Chakladar, J. et al. The liver microbiome is implicated in cancer prognosis and modulated by alcohol and hepatitis B. Cancers (Basel) 12, 1642 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Grierson, J., Flies, E. J., Bissett, A., Ammitzboll, H. & Jones, P. Which soil microbiome? Bacteria, fungi, and protozoa communities show different relationships with urban green space type and use-intensity. Sci. Total Environ. 863, 160468 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, X., Xia, Y., He, F., Zhu, C. & Ren, W. Intestinal mycobiota in health and diseases: from a disrupted equilibrium to clinical opportunities. Microbiome 9, 60 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Berg, G. et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome 8, 103 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • El-Sayed, A., Aleya, L. & Kamel, M. Microbiota’s role in health and diseases. Environ. Sci. Pollut. Res. Int. 28, 36967–36983 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marchesi, J. R. & Ravel, J. The vocabulary of microbiome research: a proposal. Microbiome 3, 31 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rajendhran, J. & Gunasekaran, P. Microbial phylogeny and diversity: small subunit ribosomal RNA sequence analysis and beyond. Microbiol. Res. 166, 99–110 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kumar, P. S. Microbiomics: were we all wrong before? Periodontol 2000 85, 8–11 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Dominguez-Bello, M. G., Godoy-Vitorino, F., Knight, R. & Blaser, M. J. Role of the microbiome in human development. Gut 68, 1108–1114 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Turnbaugh, P. J. et al. The human microbiome project. Nature 449, 804–810 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Proctor, L. M. The National Institutes of Health Human Microbiome Project. Semin. Fetal Neonatal Med. 21, 368–372 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Integrative, H.M.P.R.N.C. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 16, 276–289 (2014).

    Article 

    Google Scholar
     

  • Gilbert, J. A. et al. The Earth Microbiome Project: Meeting report of the “1 EMP meeting on sample selection and acquisition” at Argonne National Laboratory October 6 2010. Stand Genom. Sci. 3, 249–253 (2010).

    Article 

    Google Scholar
     

  • Gilbert, J. A., Jansson, J. K. & Knight, R. The Earth Microbiome project: successes and aspirations. BMC Biol. 12, 69 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McCoubrey, L. E., Gaisford, S., Orlu, M. & Basit, A. W. Predicting drug-microbiome interactions with machine learning. Biotechnol. Adv. 54, 107797 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pryor, R., Martinez-Martinez, D., Quintaneiro, L. & Cabreiro, F. The role of the microbiome in drug response. Annu. Rev. Pharm. Toxicol. 60, 417–435 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Kamath, S., Stringer, A. M., Prestidge, C. A. & Joyce, P. Targeting the gut microbiome to control drug pharmacomicrobiomics: the next frontier in oral drug delivery. Expert Opin. Drug Deliv. 7, 1–17 (2023).

    Article 

    Google Scholar
     

  • Becker, H. E. F., Demers, K., Derijks, L. J. J., Jonkers, D. & Penders, J. Current evidence and clinical relevance of drug-microbiota interactions in inflammatory bowel disease. Front. Microbiol. 14, 1107976 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rizkallah, M. R., Saad, R. & Aziz, R. K. The Human Microbiome Project, personalized medicine and the birth of pharmacomicrobiomics. Curr. Pharm. Pers. Med. 8, 182–193 (2010).

    CAS 

    Google Scholar
     

  • Clayton, T. A. et al. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature 440, 1073–1077 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nicholson, J. K., Wilson, I. D. & Lindon, J. C. Pharmacometabonomics as an effector for personalized medicine. Pharmacogenomics 12, 103–111 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nayak, R. R. & Turnbaugh, P. J. Mirror, mirror on the wall: which microbiomes will help heal them all? BMC Med. 14, 72 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Balasopoulou, A., Patrinos, G. P. & Katsila, T. Pharmacometabolomics informs viromics toward precision medicine. Front. Pharm. 7, 411 (2016).

    Article 

    Google Scholar
     

  • Katsila, T., Balasopoulou, A., Tsagaraki, I. & Patrinos, G. P. Pharmacomicrobiomics informs clinical pharmacogenomics. Pharmacogenomics 20, 731–739 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wilson, I. D. Drugs, bugs, and personalized medicine: pharmacometabonomics enters the ring. Proc. Natl Acad. Sci. USA 106, 14187–14188 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fu, J. et al. Pharmacometabonomics: data processing and statistical analysis. Brief. Bioinform. 22, bbab138 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Everett, J. R. From metabonomics to pharmacometabonomics: the role of metabolic profiling in personalized medicine. Front. Pharm. 7, 297 (2016).

    Article 

    Google Scholar
     

  • Sorbara, M. T. & Pamer, E. G. Microbiome-based therapeutics. Nat. Rev. Microbiol. 20, 365–380 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wainwright, M. & Kristiansen, J. E. On the 75th anniversary of Prontosil. Dyes Pigments 88, 231–234 (2010).

    Article 

    Google Scholar
     

  • Bentley, R. Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence beta-lactams). J. Ind. Microbiol. Biotechnol. 36, 775–786 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Paranjape, K. et al. Unravelling the importance of the eukaryotic and bacterial communities and their relationship with Legionella spp. ecology in cooling towers: a complex network. Microbiome 8, 157 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lepage, P. et al. A metagenomic insight into our gut’s microbiome. Gut 62, 146–158 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Valles-Colomer, M. et al. Meta-omics in inflammatory bowel disease research: applications, challenges, and guidelines. J. Crohns Colitis 10, 735–746 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Sha, G. et al. Integrated meta-omics study on rapid tylosin removal mechanism and dynamics of antibiotic resistance genes during aerobic thermophilic fermentation of tylosin mycelial dregs. Bioresour. Technol. 351, 127010 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McDaniel, E. A. et al. Prospects for multi-omics in the microbial ecology of water engineering. Water Res. 205, 117608 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kaddurah-Daouk, R. & Weinshilboum, R. M. Pharmacometabolomics Research Network Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology. Clin. Pharm. Ther. 95, 154–167 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Kaddurah-Daouk, R., Kristal, B. S. & Weinshilboum, R. M. Metabolomics: a global biochemical approach to drug response and disease. Annu. Rev. Pharm. Toxicol. 48, 653–683 (2008).

    Article 
    CAS 

    Google Scholar
     

  • Nicholson, J. K. & Wilson, I. D. Opinion: understanding ‘global’ systems biology: metabonomics and the continuum of metabolism. Nat. Rev. Drug Discov. 2, 668–676 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beger, R. D., Schmidt, M. A. & Kaddurah-Daouk, R. Current concepts in pharmacometabolomics, biomarker discovery, and precision medicine. Metabolites 10, 129 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Everett, J. R., Loo, R. L. & Pullen, F. S. Pharmacometabonomics and personalized medicine. Ann. Clin. Biochem. 50, 523–545 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Everett, J. R. Pharmacometabonomics in humans: a new tool for personalized medicine. Pharmacogenomics 16, 737–754 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rosato, A. et al. From correlation to causation: analysis of metabolomics data using systems biology approaches. Metabolomics 14, 37 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McWhinney, S. R. & McLeod, H. L. Using germline genotype in cancer pharmacogenetic studies. Pharmacogenomics 10, 489–493 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Derosa, L. et al. Microbiota-centered interventions: the next breakthrough in immuno-oncology? Cancer Discov. 11, 2396–2412 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, Y., Liu, Q. W., Liao, H. X. & Xu, W. W. Microbiota in cancer chemoradiotherapy resistance. Clin. Transl. Med. 11, e250 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Emadi, A., Jones, R. J. & Brodsky, R. A. Cyclophosphamide and cancer: golden anniversary. Nat. Rev. Clin. Oncol. 6, 638–647 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gershwin, M. E., Goetzl, E. J. & Steinberg, A. D. Cyclophosphamide: use in practice. Ann. Intern. Med. 80, 531–540 (1974).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Patel, J. M. Metabolism and pulmonary toxicity of cyclophosphamide. Pharm. Ther. 47, 137–146 (1990).

    Article 
    CAS 

    Google Scholar
     

  • Barnes, H., Holland, A. E., Westall, G. P., Goh, N. S. & Glaspole, I. N. Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst. Rev. 1, CD010908 (2018).

    PubMed 

    Google Scholar
     

  • Clemente, C. G. et al. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77, 1303–1310 (1996).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, L. et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med. 348, 203–213 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Katz, S. C. et al. T cell infiltrate predicts long-term survival following resection of colorectal cancer liver metastases. Ann. Surg. Oncol. 16, 2524–2530 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Jamiyan, T. et al. Prognostic impact of a tumor-infiltrating lymphocyte subtype in triple negative cancer of the breast. Breast Cancer 27, 880–892 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Roy, S. & Trinchieri, G. Microbiota: a key orchestrator of cancer therapy. Nat. Rev. Cancer 17, 271–285 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Viaud, S. et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients. Cancer Res. 71, 661–665 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nakahara, T. et al. Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood 115, 4384–4392 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghiringhelli, F. et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur. J. Immunol. 34, 336–344 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bracci, L. et al. Cyclophosphamide enhances the antitumor efficacy of adoptively transferred immune cells through the induction of cytokine expression, B-cell and T-cell homeostatic proliferation, and specific tumor infiltration. Clin. Cancer Res. 13, 644–653 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sistigu, A. et al. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin. Immunopathol. 33, 369–383 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hughes, E. et al. T-cell modulation by cyclophosphamide for tumour therapy. Immunology 154, 62–68 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Madondo, M. T., Quinn, M. & Plebanski, M. Low dose cyclophosphamide: mechanisms of T cell modulation. Cancer Treat. Rev. 42, 3–9 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Zhao, C. et al. Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant. J. Hematol. Oncol. 15, 64 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Toulmonde, M., Demolis, P. & Houede, N. Salvage chemotherapy for hormone-refractory prostate cancer: association of Adriamycin and ifosfamide. Exp. Ther. Med. 1, 1005–1011 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, J., Liu, K. X., Qu, J. M. & Wang, X. D. The changes induced by cyclophosphamide in intestinal barrier and microflora in mice. Eur. J. Pharm. 714, 120–124 (2013).

    Article 
    CAS 

    Google Scholar
     

  • Xu, X. & Zhang, X. Effects of cyclophosphamide on immune system and gut microbiota in mice. Microbiol. Res. 171, 97–106 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Daillere, R. et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 45, 931–943 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mego, M. et al. Prevention of irinotecan induced diarrhea by probiotics: a randomized double blind, placebo controlled pilot study. Complement Ther. Med. 23, 356–362 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Bleiberg, H. CPT-11 in gastrointestinal cancer. Eur. J. Cancer 35, 371–379 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dobi, A., Gasque, P., Guiraud, P. & Selambarom, J. Irinotecan (CPT-11) canonical anti-cancer drug can also modulate antiviral and pro-inflammatory responses of primary human synovial fibroblasts. Cells 10, 1431 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bailly, C. Irinotecan: 25 years of cancer treatment. Pharm. Res. 148, 104398 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Zhao, J. et al. In situ activation of STING pathway with polymeric SN38 for cancer chemoimmunotherapy. Biomaterials 268, 120542 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Karas, S. et al. Optimal sampling strategies for irinotecan (CPT-11) and its active metabolite (SN-38) in cancer patients. AAPS J. 22, 59 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Stringer, A. M. et al. Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol. Ther. 7, 1919–1925 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Flieger, D. et al. Phase II clinical trial for prevention of delayed diarrhea with cholestyramine/levofloxacin in the second-line treatment with irinotecan biweekly in patients with metastatic colorectal carcinoma. Oncology 72, 10–16 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kehrer, D. F. et al. Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin. Cancer Res. 7, 1136–1141 (2001).

    CAS 
    PubMed 

    Google Scholar
     

  • Leibovici, L. et al. Antibiotic prophylaxis in neutropenic patients: new evidence, practical decisions. Cancer 107, 1743–1751 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831–835 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kong, R. et al. Old drug new use-amoxapine and its metabolites as potent bacterial beta-glucuronidase inhibitors for alleviating cancer drug toxicity. Clin. Cancer Res. 20, 3521–3530 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, P. T. et al. Enhancement of CPT-11 antitumor activity by adenovirus-mediated expression of beta-glucuronidase in tumors. Cancer Gene Ther. 18, 381–389 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cheng, K. W. et al. Pharmacological inhibition of bacterial beta-glucuronidase prevents irinotecan-induced diarrhea without impairing its antitumor efficacy in vivo. Pharm. Res. 139, 41–49 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Chamseddine, A. N. et al. Intestinal bacterial beta-glucuronidase as a possible predictive biomarker of irinotecan-induced diarrhea severity. Pharm. Ther. 199, 1–15 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Gallotti, B. et al. Effects of dietary fibre intake in chemotherapy-induced mucositis in murine model. Br. J. Nutr. 126, 853–864 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Takasuna, K. et al. Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res. 56, 3752–3757 (1996).

    CAS 
    PubMed 

    Google Scholar
     

  • Songjang, W. et al. Tumor-promoting activity and proteomic profiling of cisplatin/oxaliplatin-derived DAMPs in cholangiocarcinoma cells. Int J. Mol. Sci. 23, 10540 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Skripova, V., Vlasenkova, R., Zhou, Y., Astsaturov, I. & Kiyamova, R. Identification of new regulators of pancreatic cancer cell sensitivity to oxaliplatin and cisplatin. Molecules 27, 1289 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, C., Xu, C., Gao, X. & Yao, Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics 12, 2115–2132 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yamada, Y. et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naive patients with advanced gastric cancer. Ann. Oncol. 26, 141–148 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vaisman, A., Masutani, C., Hanaoka, F. & Chaney, S. G. Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase eta. Biochemistry 39, 4575–4580 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cruet-Hennequart, S., Glynn, M. T., Murillo, L. S., Coyne, S. & Carty, M. P. Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin. DNA Repair (Amst.) 7, 582–596 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lokody, I. Tumour microenvironment: bacterial balance affects cancer treatment. Nat. Rev. Cancer 14, 10 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roberti, M. P. et al. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. Nat. Med. 26, 919–931 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bachem, A. et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8(+) T cells. Immunity 51, 285–297 e5 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, Y. et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8(+) T cell immunity. Cell Metab. 33, 988–1000 e7 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qin, S. et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol. Cancer 18, 155 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andrews, L. P., Yano, H. & Vignali, D. A. A. Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups. Nat. Immunol. 20, 1425–1434 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Burugu, S., Dancsok, A. R. & Nielsen, T. O. Emerging targets in cancer immunotherapy. Semin Cancer Biol. 52, 39–52 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chaput, N. et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann. Oncol. 28, 1368–1379 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Helmink, B. A. et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature 577, 549–555 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Poore, G. D. et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature 579, 567–574 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Costea, P. I. et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 35, 1069–1076 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tam, V. et al. Benefits and limitations of genome-wide association studies. Nat. Rev. Genet 20, 467–484 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Baruch, E. N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371, 602–609 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Davar, D. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 371, 595–602 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jamison, D. T. et al. Disease Control Priorities in Developing Countries. 2nd edition. Washington (DC): The International Bank for Reconstruction and Development/ The World Bank (2006).

  • Ruan, Y. et al. Cardiovascular disease (CVD) and associated risk factors among older adults in six low-and middle-income countries: results from SAGE Wave 1. BMC Public Health 18, 778 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nitsa, A. et al. Vitamin D in cardiovascular disease. Vivo 32, 977–981 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Roth, G. A. et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J. Am. Coll. Cardiol. 70, 1–25 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zuo, H. L. et al. Interactions of antithrombotic herbal medicines with Western cardiovascular drugs. Pharm. Res. 159, 104963 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Curini, L. & Amedei, A. Cardiovascular diseases and pharmacomicrobiomics: a perspective on possible treatment relevance. Biomedicines 9, 1338 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kyoung, J., Atluri, R. R. & Yang, T. Resistance to antihypertensive drugs: is gut microbiota the missing link? Hypertension 79, 2138–2147 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chakaroun, R. M., Olsson, L. M. & Backhed, F. The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease. Nat. Rev. Cardiol. 20, 217–235 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Yang, Z. et al. Gut microbiota and hypertension: association, mechanisms and treatment. Clin. Exp. Hypertens. 45, 2195135 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Chen, H. Q. et al. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in antihypertensive treatment. Front. Med. (Lausanne) 8, 742394 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Pirmohamed, M. Warfarin: almost 60 years old and still causing problems. Br. J. Clin. Pharm. 62, 509–511 (2006).

    Article 

    Google Scholar
     

  • Kimmel, S. E. Warfarin pharmacogenomics: current best evidence. J. Thromb. Haemost. 13, S266–S271 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, S. et al. Warfarin and vitamin K epoxide reductase: a molecular accounting for observed inhibition. Blood 132, 647–657 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Czogalla, K. J. et al. Warfarin and vitamin K compete for binding to Phe55 in human VKOR. Nat. Struct. Mol. Biol. 24, 77–85 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, X. et al. A novel vitamin K derived anticoagulant tolerant to genetic variations of vitamin K epoxide reductase. J. Thromb. Haemost. 19, 689–700 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rishavy, M. A. et al. Warfarin alters vitamin K metabolism: a surprising mechanism of VKORC1 uncoupling necessitates an additional reductase. Blood 131, 2826–2835 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wise, E. S. et al. The influence of VKORC1 and CYP2C9 mutations on warfarin response after total hip and knee arthroplasty. J. Orthop. 12, S145–S151 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jorgensen, A. L., FitzGerald, R. J., Oyee, J., Pirmohamed, M. & Williamson, P. R. Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis. PLoS One 7, e44064 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xue, L. et al. Theory-based pharmacokinetics and pharmacodynamics of S- and R-warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients. Br. J. Clin. Pharm. 83, 823–835 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Wang, L. et al. The gut microbes, Enterococcus and Escherichia-Shigella, affect the responses of heart valve replacement patients to the anticoagulant warfarin. Pharm. Res. 159, 104979 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Ward, N. C., Watts, G. F. & Eckel, R. H. Statin toxicity. Circ. Res. 124, 328–350 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lim, G. B. Statins outperform dietary supplements for LDL-C lowering. Nat. Rev. Cardiol. 20, 6 (2023).

    PubMed 

    Google Scholar
     

  • Dehnavi, S. et al. Statins and autoimmunity: state-of-the-art. Pharm. Ther. 214, 107614 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Arnett, D. K. et al. ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 140, e596–e646 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, Q. & Liao, J. K. Statins and cardiovascular diseases: from cholesterol lowering to pleiotropy. Curr. Pharm. Des. 15, 467–478 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Oesterle, A., Laufs, U. & Liao, J. K. Pleiotropic effects of statins on the cardiovascular system. Circ. Res. 120, 229–243 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, J. et al. Alterations in gut microbiota by statin therapy and possible intermediate effects on hyperglycemia and hyperlipidemia. Front. Microbiol. 10, 1947 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Caparros-Martin, J. A. et al. Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome 5, 95 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tuteja, S. & Ferguson, J. F. Gut microbiome and response to cardiovascular drugs. Circ. Genom. Precis Med. 12, 421–429 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Campbell, T. J. & MacDonald, P. S. Digoxin in heart failure and cardiac arrhythmias. Med. J. Aust. 179, 98–102 (2003).

    Article 
    PubMed 

    Google Scholar
     

  • Patocka, J., Nepovimova, E., Wu, W. & Kuca, K. Digoxin: pharmacology and toxicology-A review. Environ. Toxicol. Pharm. 79, 103400 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295–298 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saha, J. R., Butler, V. P. Jr, Neu, H. C. & Lindenbaum, J. Digoxin-inactivating bacteria: identification in human gut flora. Science 220, 325–327 (1983).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bo, J. et al. Eggerthella lenta bloodstream infections: two cases and review of the literature. Future Microbiol. 15, 981–985 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kageyama, A., Benno, Y. & Nakase, T. Phylogenetic evidence for the transfer of Eubacterium lentum to the genus Eggerthella as Eggerthella lenta gen. nov., comb. nov. Int J. Syst. Bacteriol. 49, 1725–1732 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Haiser, H. J., Seim, K. L., Balskus, E. P. & Turnbaugh, P. J. Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics. Gut Microbes 5, 233–238 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Evered, M. D., Robinson, M. M. & Richardson, M. A. Captopril given intracerebroventricularly, subcutaneously or by gavage inhibits angiotensin-converting enzyme activity in the rat brain. Eur. J. Pharm. 68, 443–449 (1980).

    Article 
    CAS 

    Google Scholar
     

  • Antunes, A. M., Guerrante, R. D., Avila, J. P., Lins Mendes, F. M. & Fierro, I. M. Case study of patents related to captopril, Squibb’s first blockbuster. Expert Opin. Ther. Pat. 26, 1449–1457 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Berecek, K. H., Reaves, P. & Raizada, M. Effects of early perturbation of the renin-angiotensin system on cardiovascular remodeling in spontaneously hypertensive rats. Vasc. Pharm. 42, 93–98 (2005).

    Article 
    CAS 

    Google Scholar
     

  • Wu, J. N. & Berecek, K. H. Prevention of genetic hypertension by early treatment of spontaneously hypertensive rats with the angiotensin converting enzyme inhibitor captopril. Hypertension 22, 139–146 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, L., Edwards, D. G. & Berecek, K. H. Effects of early captopril treatment and its removal on plasma angiotensin converting enzyme (ACE) activity and arginine vasopressin in hypertensive rats (SHR) and normotensive rats (WKY). Clin. Exp. Hypertens. 18, 201–226 (1996).

    Article 
    PubMed 

    Google Scholar
     

  • Wu, H., Lam, T. Y. C., Shum, T. F., Tsai, T. Y. & Chiou, J. Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration. Hypertens. Res. 45, 270–282 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yang, T. et al. Sustained captopril-induced reduction in blood pressure is associated with alterations in gut-brain axis in the spontaneously hypertensive rat. J. Am. Heart Assoc. 8, e010721 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, T., Richards, E. M., Pepine, C. J. & Raizada, M. K. The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nat. Rev. Nephrol. 14, 442–456 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Santisteban, M. M., Kim, S., Pepine, C. J. & Raizada, M. K. Brain-gut-bone marrow axis: implications for hypertension and related therapeutics. Circ. Res. 118, 1327–1336 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. B., Yang, T., Richards, E. M., Pepine, C. J. & Raizada, M. K. Maternal treatment with captopril persistently alters gut-brain communication and attenuates hypertension of male offspring. Hypertension 75, 1315–1324 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qi, Y., Aranda, J. M., Rodriguez, V., Raizada, M. K. & Pepine, C. J. Impact of antibiotics on arterial blood pressure in a patient with resistant hypertension—a case report. Int J. Cardiol. 201, 157–158 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Angiotensin-Converting Enzyme Inhibitors. in LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Bethesda, 2012).

  • Wang, B. L., Pan, D. Q., Zhou, K. L., Lou, Y. Y. & Shi, J. H. Multi-spectroscopic approaches and molecular simulation research of the intermolecular interaction between the angiotensin-converting enzyme inhibitor (ACE inhibitor) benazepril and bovine serum albumin (BSA). Spectrochim. Acta A Mol. Biomol. Spectrosc. 212, 15–24 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hou, F. F. et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N. Engl. J. Med. 354, 131–140 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Senthong, V. et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J. Am. Heart Assoc. 5, e002816 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, X. S. et al. Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors. Eur. Heart J. 38, 814–824 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, W. H. et al. Increased trimethylamine N-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus. Clin. Chem. 63, 297–306 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Konop, M. et al. Enalapril decreases rat plasma concentration of TMAO, a gut bacteria-derived cardiovascular marker. Biomarkers 23, 380–385 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Romano, K. A., Vivas, E. I., Amador-Noguez, D. & Rey, F. E. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio 6, e02481 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Craciun, S. & Balskus, E. P. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc. Natl Acad. Sci. USA 109, 21307–21312 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nowinski, A. & Ufnal, M. Trimethylamine N-oxide: a harmful, protective or diagnostic marker in lifestyle diseases? Nutrition 46, 7–12 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jaworska, K. et al. Hypertension in rats is associated with an increased permeability of the colon to TMA, a gut bacteria metabolite. PLoS One 12, e0189310 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qi, X., Yun, C., Pang, Y. & Qiao, J. The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes 13, 1–21 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Cornejo-Pareja, I., Munoz-Garach, A., Clemente-Postigo, M. & Tinahones, F. J. Importance of gut microbiota in obesity. Eur. J. Clin. Nutr. 72, 26–37 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pascale, A. et al. Microbiota and metabolic diseases. Endocrine 61, 357–371 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Neuman, H., Debelius, J. W., Knight, R. & Koren, O. Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol. Rev. 39, 509–521 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Han, Y. et al. Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol. 18, 96 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • LaMoia, T. E. & Shulman, G. I. Cellular and molecular mechanisms of metformin action. Endocr. Rev. 42, 77–96 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Giusti, L. et al. The protective action of metformin against pro-inflammatory cytokine-induced human islet cell damage and the mechanisms involved. Cells 11, 2465 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sundelin, E., Jensen, J. B., Jakobsen, S., Gormsen, L. C. & Jessen, N. Metformin biodistribution: a key to mechanisms of action? J. Clin. Endocrinol. Metab. 105, dgaa332 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Minamii, T., Nogami, M. & Ogawa, W. Mechanisms of metformin action: in and out of the gut. J. Diabetes Investig. 9, 701–703 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rena, G., Hardie, D. G. & Pearson, E. R. The mechanisms of action of metformin. Diabetologia 60, 1577–1585 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Foretz, M., Guigas, B. & Viollet, B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat. Rev. Endocrinol. 15, 569–589 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850–858 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sun, L. et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat. Med. 24, 1919–1929 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bryrup, T. et al. Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study. Diabetologia 62, 1024–1035 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pollak, M. The effects of metformin on gut microbiota and the immune system as research frontiers. Diabetologia 60, 1662–1667 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Duca, F. A. et al. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. Nat. Med. 21, 506–511 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luo, F. et al. Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovasc. Diabetol. 18, 54 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dalile, B., Van Oudenhove, L., Vervliet, B. & Verbeke, K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol. 16, 461–478 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Agrawal, N., Sharma, M., Singh, S. & Goyal, A. Recent advances of alpha-glucosidase inhibitors: a comprehensive review. Curr. Top. Med. Chem. 22, 2069–2086 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dhameja, M. & Gupta, P. Synthetic heterocyclic candidates as promising alpha-glucosidase inhibitors: an overview. Eur. J. Med. Chem. 176, 343–377 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, X. et al. Effects of acarbose on the gut microbiota of prediabetic patients: a randomized, double-blind, controlled crossover trial. Diabetes Ther. 8, 293–307 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brunkhorst, C., Andersen, C. & Schneider, E. Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli. J. Bacteriol. 181, 2612–2619 (1999).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yadav, H., Jain, S. & Sinha, P. R. Effect of Dahi containing Lactococcus lactis on the progression of diabetes induced by a high-fructose diet in rats. Biosci. Biotechnol. Biochem. 70, 1255–1258 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yadav, H., Jain, S. & Sinha, P. R. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition 23, 62–68 (2007).

    Article 
    PubMed 

    Google Scholar
     

  • Kaushal, D. & Kansal, V. K. Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum improves phagocytic potential of macrophages in aged mice. J. Food Sci. Technol. 51, 1147–1153 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Su, B. et al. Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus. J. Diabetes 7, 729–739 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maruhama, Y. et al. Effects of a glucoside-hydrolase inhibitor (Bay g 5421) on serum lipids, lipoproteins and bile acids, fecal fat and bacterial flora, and intestinal gas production in hyperlipidemic patients. Tohoku J. Exp. Med. 132, 453–462 (1980).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kishida, Y., Okubo, H., Ohno, H., Oki, K. & Yoneda, M. Effect of miglitol on the suppression of nonalcoholic steatohepatitis development and improvement of the gut environment in a rodent model. J. Gastroenterol. 52, 1180–1191 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Drucker, D. J. & Nauck, M. A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368, 1696–1705 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Meier, J. J. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 8, 728–742 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Drucker, D. J. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 27, 740–756 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Baggio, L. L. & Drucker, D. J. Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight. J. Clin. Invest. 124, 4223–4226 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tolhurst, G. et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364–371 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kimura, I. et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4, 1829 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Vettorazzi, J. F. et al. The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells. Metabolism 65, 54–63 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aoki, R. et al. A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation. Sci. Rep. 7, 43522 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, L., Li, P., Tang, Z., Yan, X. & Feng, B. Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment. Sci. Rep. 6, 33251 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Q. et al. Featured article: structure moderation of gut microbiota in liraglutide-treated diabetic male rats. Exp. Biol. Med. (Maywood) 243, 34–44 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, L. et al. A glucagon-like peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota. Front. Endocrinol. (Lausanne) 9, 233 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Charpentier, J. et al. Liraglutide targets the gut microbiota and the intestinal immune system to regulate insulin secretion. Acta Diabetol. 58, 881–897 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shang, J. et al. Liraglutide-induced structural modulation of the gut microbiota in patients with type 2 diabetes mellitus. PeerJ 9, e11128 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yuan, X. et al. Identification of therapeutic effect of glucagon-like peptide 1 in the treatment of STZ-induced diabetes mellitus in rats by restoring the balance of intestinal flora. J. Cell Biochem. 119, 10067–10074 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Handelsman, Y. et al. American association of clinical endocrinologists and american college of endocrinology—clinical practice guidelines for developing a diabetes mellitus comprehensive care plan – 2015. Endocr. Pract. 21, 1–87 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Olivares, M. et al. The potential role of the dipeptidyl peptidase-4-like activity from the gut microbiota on the host health. Front. Microbiol. 9, 1900 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liao, X. et al. Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis. EBioMedicine 44, 665–674 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yan, X., Feng, B., Li, P., Tang, Z. & Wang, L. Microflora disturbance during progression of glucose intolerance and effect of sitagliptin: an animal study. J. Diabetes Res. 2016, 2093171 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Q. et al. Vildagliptin increases butyrate-producing bacteria in the gut of diabetic rats. PLoS One 12, e0184735 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, X. et al. Host-microbiota interaction-mediated resistance to inflammatory bowel disease in pigs. Microbiome 10, 115 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alshehri, D. et al. Dysbiosis of gut microbiota in inflammatory bowel disease: current therapies and potential for microbiota-modulating therapeutic approaches. Bosn. J. Basic Med. Sci. 21, 270–283 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nilsson, A. et al. Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study. Am. J. Gastroenterol. 90, 381–387 (1995).

    CAS 
    PubMed 

    Google Scholar
     

  • Kim, D. H. Gut microbiota-mediated drug-antibiotic interactions. Drug Metab. Dispos. 43, 1581–1589 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Azad Khan, A. K., Guthrie, G., Johnston, H. H., Truelove, S. C. & Williamson, D. H. Tissue and bacterial splitting of sulphasalazine. Clin. Sci. (Lond.) 64, 349–354 (1983).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, H. J., Zhang, H., Orlovich, D. A. & Fawcett, J. P. The influence of probiotic treatment on sulfasalazine metabolism in rat. Xenobiotica 42, 791–797 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Crouwel, F., Buiter, H. J. C. & de Boer, N. K. Gut microbiota-driven drug metabolism in inflammatory bowel disease. J. Crohns Colitis 15, 307–315 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savarino, V. et al. The appropriate use of proton-pump inhibitors. Minerva Med 109, 386–399 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Graham, D. Y. & Tansel, A. Interchangeable use of proton pump inhibitors based on relative potency. Clin. Gastroenterol. Hepatol. 16, 800–808.e7 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pinto-Sanchez, M. I., Yuan, Y., Bercik, P. & Moayyedi, P. Proton pump inhibitors for functional dyspepsia. Cochrane Database Syst. Rev. 3, CD011194 (2017).

    PubMed 

    Google Scholar
     

  • Forgacs, I. & Loganayagam, A. Overprescribing proton pump inhibitors. BMJ 336, 2–3 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Akram, F., Huang, Y., Lim, V., Huggan, P. J. & Merchant, R. A. Proton pump inhibitors: are we still prescribing them without valid indications? Australas. Med. J. 7, 465–470 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Eid, S. M. et al. Patterns and predictors of proton pump inhibitor overuse among academic and non-academic hospitalists. Intern Med. 49, 2561–2568 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • Bonder, M. J. et al. The influence of a short-term gluten-free diet on the human gut microbiome. Genome Med. 8, 45 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jackson, M. A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749–756 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Imhann, F. et al. Proton pump inhibitors affect the gut microbiome. Gut 65, 740–748 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Freedberg, D. E. et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial. Gastroenterology 149, 883–885.e9 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Buffie, C. G. & Pamer, E. G. Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13, 790–801 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leonard, J., Marshall, J. K. & Moayyedi, P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am. J. Gastroenterol. 102, 2047–2056 (2007).

    Article 
    PubMed 

    Google Scholar
     

  • Baur, D. et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect. Dis. 17, 990–1001 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Bajaj, J. S. et al. Proton pump inhibitor initiation and withdrawal affects gut microbiota and readmission risk in cirrhosis. Am. J. Gastroenterol. 113, 1177–1186 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Stark, C. M., Susi, A., Emerick, J. & Nylund, C. M. Antibiotic and acid-suppression medications during early childhood are associated with obesity. Gut 68, 62–69 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Harirforoosh, S., Asghar, W. & Jamali, F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J. Pharm. Pharm. Sci. 16, 821–847 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Sostres, C., Gargallo, C. J. & Lanas, A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res. Ther. 15, S3 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Higuchi, K. et al. Present status and strategy of NSAIDs-induced small bowel injury. J. Gastroenterol. 44, 879–888 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Petruzzelli, M. et al. Intestinal mucosal damage caused by non-steroidal anti-inflammatory drugs: role of bile salts. Clin. Biochem. 40, 503–510 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Boelsterli, U. A., Redinbo, M. R. & Saitta, K. S. Multiple NSAID-induced hits injure the small intestine: underlying mechanisms and novel strategies. Toxicol. Sci. 131, 654–667 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yauw, S. T. K. et al. Microbial glucuronidase inhibition reduces severity of diclofenac-induced anastomotic leak in rats. Surg. Infect. (Larchmt.) 19, 417–423 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Dashnyam, P. et al. beta-Glucuronidases of opportunistic bacteria are the major contributors to xenobiotic-induced toxicity in the gut. Sci. Rep. 8, 16372 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ervin, S. M. et al. Targeting regorafenib-induced toxicity through inhibition of gut microbial beta-glucuronidases. ACS Chem. Biol. 14, 2737–2744 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, B., Liu, H., Yang, J., Gupta, V. K. & Jiang, Y. New insights on bioactivities and biosynthesis of flavonoid glycosides. Trends Food Sci. Technol. 79, 116–124 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dinan, T. G. & Cryan, J. F. The microbiome-gut-brain axis in health and disease. Gastroenterol. Clin. North Am. 46, 77–89 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • LeWitt, P. A. Levodopa therapy for Parkinson’s disease: pharmacokinetics and pharmacodynamics. Mov. Disord. 30, 64–72 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Marsot, A., Guilhaumou, R., Azulay, J. P. & Blin, O. Levodopa in Parkinson’s disease: a review of population pharmacokinetics/pharmacodynamics analysis. J. Pharm. Pharm. Sci. 20, 226–238 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • van Kessel, S. P. et al. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nat. Commun. 10, 310 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J. & Balskus, E. P. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science 364, eaau6323 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Musil, V., Blankova, A. & Baca, V. A plea for an extension of the anatomical nomenclature: the locomotor system. Bosn. J. Basic Med. Sci. 18, 117–125 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Peretti, S. et al. The Yin-Yang pharmacomicrobiomics on treatment response in inflammatory arthritides: a narrative review. Genes (Basel) 14, 89 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Zhao, S. et al. Drug repurposing by siderophore conjugation: synthesis and biological evaluation of siderophore-methotrexate conjugates as antibiotics. Angew. Chem. Int. Ed. Engl. 61, e202204139 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Romao, V. C., Lima, A., Bernardes, M., Canhao, H. & Fonseca, J. E. Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity? Immunol. Res. 60, 289–310 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ramos-Romero, S. et al. Mechanistically different effects of fat and sugar on insulin resistance, hypertension, and gut microbiota in rats. Am. J. Physiol. Endocrinol. Metab. 314, E552–E563 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dunn, C. J. & Peters, D. H. Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 49, 721–749 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, B. et al. Induction and amelioration of methotrexate-induced gastrointestinal toxicity are related to immune response and gut microbiota. EBioMedicine 33, 122–133 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sayers, E., MacGregor, A. & Carding, S. R. Drug-microbiota interactions and treatment response: relevance to rheumatoid arthritis. AIMS Microbiol. 4, 642–654 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, X. et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 21, 895–905 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goodman, S. M., Cronstein, B. N. & Bykerk, V. P. Outcomes related to methotrexate dose and route of administration in patients with rheumatoid arthritis: a systematic literature review. Clin. Exp. Rheumatol. 33, 272–278 (2015).

    PubMed 

    Google Scholar
     

  • Halilova, K. I. et al. Markers of treatment response to methotrexate in rheumatoid arthritis: where do we stand? Int. J. Rheumatol. 2012, 978396 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Angelis-Stoforidis, P., Vajda, F. J. & Christophidis, N. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis. Clin. Exp. Rheumatol. 17, 313–320 (1999).

    CAS 
    PubMed 

    Google Scholar
     

  • Dervieux, T. et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 50, 2766–2774 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clemens, J. Q. Infection and inflammation of the genitourinary tract. J. Urol. 208, 455 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Choi, E., Buie, J., Camacho, J., Sharma, P. & de Riese, W. T. W. Evolution of androgen deprivation therapy (ADT) and its new emerging modalities in prostate cancer: an update for practicing urologists, clinicians and medical providers. Res. Rep. Urol. 14, 87–108 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Terrisse, S. et al. Immune system and intestinal microbiota determine efficacy of androgen deprivation therapy against prostate cancer. J. Immunother. Cancer 10, e004191 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Daisley, B. A. et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Nat. Commun. 11, 4822 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sfanos, K. S., Yegnasubramanian, S., Nelson, W. G. & De Marzo, A. M. The inflammatory microenvironment and microbiome in prostate cancer development. Nat. Rev. Urol. 15, 11–24 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • McCulloch, J. A. & Trinchieri, G. Gut bacteria enable prostate cancer growth. Science 374, 154–155 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dickson, R. P., Erb-Downward, J. R., Martinez, F. J. & Huffnagle, G. B. The microbiome and the respiratory tract. Annu Rev. Physiol. 78, 481–504 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Unger, S. A. & Bogaert, D. The respiratory microbiome and respiratory infections. J. Infect. 74, S84–S88 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Man, W. H., de Steenhuijsen Piters, W. A. & Bogaert, D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat. Rev. Microbiol. 15, 259–270 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mi, J. et al. The research progress in immunotherapy of tuberculosis. Front. Cell Infect. Microbiol. 11, 763591 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bermingham, W. H. et al. Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs. Clin. Exp. Allergy 52, 375–386 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Namasivayam, S. et al. Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy. Microbiome 5, 71 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Naidoo, C. C. et al. The microbiome and tuberculosis: state of the art, potential applications, and defining the clinical research agenda. Lancet Respir. Med. 7, 892–906 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Wipperman, M. F. et al. Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed. Sci. Rep. 7, 10767 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shen, Y. et al. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12, 509–520 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Larsen, J. M. The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology 151, 363–374 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wells, J. M. Immunomodulatory mechanisms of lactobacilli. Micro. Cell Fact. 10, S17 (2011).

    Article 

    Google Scholar
     

  • Scriba, T. J. et al. Differential recognition of mycobacterium tuberculosis-specific epitopes as a function of tuberculosis disease history. Am. J. Respir. Crit. Care Med. 196, 772–781 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hawn, T. R., Matheson, A. I., Maley, S. N. & Vandal, O. Host-directed therapeutics for tuberculosis: can we harness the host? Microbiol. Mol. Biol. Rev. 77, 608–627 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Caballero-Flores, G., Pickard, J. M. & Nunez, G. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat. Rev. Microbiol. 21, 347–360 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gong, X. et al. The interactions between gut microbiota and bioactive ingredients of traditional Chinese medicines: a review. Pharm. Res. 157, 104824 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Hayase, E. & Jenq, R. R. Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer. Genome Med. 13, 107 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Peng, Y. et al. Role of gut microbiota in travel-related acquisition of extended spectrum beta-lactamase-producing Enterobacteriaceae. J. Travel Med. 28, taab022 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • He, Z. et al. Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum beta-lactamase-producing enteroaggregative Escherichia coli infection. Microbiome 10, 79 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smet, A. et al. Broad-spectrum beta-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health. FEMS Microbiol. Rev. 34, 295–316 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Piewngam, P. et al. Composition of the intestinal microbiota in extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers and non-carriers in Thailand. Int J. Antimicrob. Agents 53, 435–441 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McCulloch, J. A. et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. Nat. Med. 28, 545–556 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Munier, A. L. et al. Comparative dynamics of the emergence of fluoroquinolone resistance in staphylococci from the nasal microbiota of patients treated with fluoroquinolones according to their environment. Int J. Antimicrob. Agents 46, 653–659 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • de Lastours, V. & Fantin, B. Impact of fluoroquinolones on human microbiota. Focus on the emergence of antibiotic resistance. Future Microbiol. 10, 1241–1255 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Klunemann, M. et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature 597, 533–538 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abt, M. C., McKenney, P. T. & Pamer, E. G. Clostridium difficile colitis: pathogenesis and host defence. Nat. Rev. Microbiol. 14, 609–620 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • O’Grady, K., Knight, D. R. & Riley, T. V. Antimicrobial resistance in Clostridioides difficile. Eur. J. Clin. Microbiol. Infect. Dis. 40, 2459–2478 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Gil, F. & Paredes-Sabja, D. Acyldepsipeptide antibiotics as a potential therapeutic agent against Clostridium difficile recurrent infections. Future Microbiol. 11, 1179–1189 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, X., Chen, Y., Zhang, S. & Dong, L. Gut microbiota-mediated immunomodulation in tumor. J. Exp. Clin. Cancer Res. 40, 221 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Simpson, R. C. et al. Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome. Nat. Med. 28, 2344–2352 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cheng, W. Y., Wu, C. Y. & Yu, J. The role of gut microbiota in cancer treatment: friend or foe? Gut 69, 1867–1876 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, X., Zhang, S., Guo, G., Han, J. & Yu, J. Gut microbiome in modulating immune checkpoint inhibitors. EBioMedicine 82, 104163 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu, Y. et al. Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies. J. Hematol. Oncol. 15, 47 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paone, P. & Cani, P. D. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut 69, 2232–2243 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Takiishi, T., Fenero, C. I. M. & Camara, N. O. S. Intestinal barrier and gut microbiota: shaping our immune responses throughout life. Tissue Barriers 5, e1373208 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ianiro, G., Tilg, H. & Gasbarrini, A. Antibiotics as deep modulators of gut microbiota: between good and evil. Gut 65, 1906–1915 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Becattini, S., Taur, Y. & Pamer, E. G. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol. Med. 22, 458–478 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Akbarali, H. I. & Dewey, W. L. Gastrointestinal motility, dysbiosis and opioid-induced tolerance: is there a link? Nat. Rev. Gastroenterol. Hepatol. 16, 323–324 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kurz, A. & Sessler, D. I. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 63, 649–671 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mora, A. L. et al. Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection. Am. J. Med. Sci. 343, 277–280 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Zhuang, Y. P. et al. Gut microbiota interactions with antitumor immunity in colorectal cancer: from understanding to application. Biomed. Pharmacother. 165, 115040 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pezo, R. C., Wong, M. & Martin, A. Impact of the gut microbiota on immune checkpoint inhibitor-associated toxicities. Ther. Adv. Gastroenterol. 12, 1756284819870911 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Bai, Z. et al. Aspirin ameliorates atherosclerotic immuno-inflammation through regulating the Treg/Th17 axis and CD39-CD73 adenosine signaling via remodeling the gut microbiota in ApoE(-/-) mice. Int. Immunopharmacol. 120, 110296 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kolodziejczyk, A. A., Zheng, D. & Elinav, E. Diet-microbiota interactions and personalized nutrition. Nat. Rev. Microbiol. 17, 742–753 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zmora, N., Suez, J. & Elinav, E. You are what you eat: diet, health and the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 16, 35–56 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sanders, M. E., Merenstein, D. J., Reid, G., Gibson, G. R. & Rastall, R. A. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat. Rev. Gastroenterol. Hepatol. 16, 605–616 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Lim, H. et al. Artificial intelligence approaches to human-microbiome protein-protein interactions. Curr. Opin. Struct. Biol. 73, 102328 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cammarota, G. et al. Gut microbiome, big data and machine learning to promote precision medicine for cancer. Nat. Rev. Gastroenterol. Hepatol. 17, 635–648 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Vitetta, L., Coulson, S., Linnane, A. W. & Butt, H. The gastrointestinal microbiome and musculoskeletal diseases: a beneficial role for probiotics and prebiotics. Pathogens 2, 606–626 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bermudez-Brito, M., Plaza-Diaz, J., Munoz-Quezada, S., Gomez-Llorente, C. & Gil, A. Probiotic mechanisms of action. Ann. Nutr. Metab. 61, 160–174 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gupta, S., Allen-Vercoe, E. & Petrof, E. O. Fecal microbiota transplantation: in perspective. Ther. Adv. Gastroenterol. 9, 229–239 (2016).

    Article 

    Google Scholar
     

  • Ser, H. L., Letchumanan, V., Goh, B. H., Wong, S. H. & Lee, L. H. The use of fecal microbiome transplant in treating human diseases: too early for poop? Front. Microbiol. 12, 519836 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Khoruts, A. Fecal microbiota transplantation-early steps on a long journey ahead. Gut Microbes 8, 199–204 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van Nood, E., Speelman, P., Nieuwdorp, M. & Keller, J. Fecal microbiota transplantation: facts and controversies. Curr. Opin. Gastroenterol. 30, 34–39 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Borody, T. J. & Campbell, J. Fecal microbiota transplantation: techniques, applications, and issues. Gastroenterol. Clin. North Am. 41, 781–803 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Li, M. et al. Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells. Eur. J. Pharm. 831, 52–59 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Lin, D. M., Koskella, B. & Lin, H. C. Phage therapy: an alternative to antibiotics in the age of multi-drug resistance. World J. Gastrointest. Pharm. Ther. 8, 162–173 (2017).

    Article 

    Google Scholar
     

  • Bourdin, G. et al. Coverage of diarrhoea-associated Escherichia coli isolates from different origins with two types of phage cocktails. Micro. Biotechnol. 7, 165–176 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Ackermann, H. W. The first phage electron micrographs. Bacteriophage 1, 225–227 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rakhuba, D. V., Kolomiets, E. I., Dey, E. S. & Novik, G. I. Bacteriophage receptors, mechanisms of phage adsorption and penetration into host cell. Pol. J. Microbiol. 59, 145–155 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Motlagh, A. M., Bhattacharjee, A. S. & Goel, R. Biofilm control with natural and genetically-modified phages. World J. Microbiol Biotechnol. 32, 67 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Ramachandran, G. & Bikard, D. Editing the microbiome the CRISPR way. Philos. Trans. R. Soc. Lond. B Biol. Sci. 374, 20180103 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reyes, A., Wu, M., McNulty, N. P., Rohwer, F. L. & Gordon, J. I. Gnotobiotic mouse model of phage-bacterial host dynamics in the human gut. Proc. Natl Acad. Sci. USA 110, 20236–20241 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lusiak-Szelachowska, M., Weber-Dabrowska, B., Jonczyk-Matysiak, E., Wojciechowska, R. & Gorski, A. Bacteriophages in the gastrointestinal tract and their implications. Gut Pathog. 9, 44 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Divya Ganeshan, S. & Hosseinidoust, Z. Phage therapy with a focus on the human microbiota. Antibiotics (Basel) 8, 131 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Ren, Z. et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut 68, 1014–1023 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Scott, A. J. et al. International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis. Gut 68, 1624–1632 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rao, B. C. et al. Human microbiome is a diagnostic biomarker in hepatocellular carcinoma. Hepatobiliary Pancreat. Dis. Int. 19, 109–115 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kuntz, T. M. & Gilbert, J. A. Introducing the microbiome into precision medicine. Trends Pharm. Sci. 38, 81–91 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rizkallah, M. R., Saad, R. & Aziz, R. K. The Human Microbiome Project, personalized medicine and the birth of phar macomicrobiomics. Curr. Pharm. Pers. Med. 8, 182–193 (2010).

    CAS 

    Google Scholar