{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:31:01Z","timestamp":1787574661204,"version":"build-2736575974"},"reference-count":105,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Pharmacy of the University of Coimbra and co-funded by the EU Recovery and Resilience Facility and Portuguese national funds","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and co-funded by the EU Recovery and Resilience Facility and Portuguese national funds","award":["UID\/PRR\/04539\/2025"],"award-info":[{"award-number":["UID\/PRR\/04539\/2025"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and co-funded by the EU Recovery and Resilience Facility and Portuguese national funds","award":["UID\/04539\/2025"],"award-info":[{"award-number":["UID\/04539\/2025"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and co-funded by the EU Recovery and Resilience Facility and Portuguese national funds","award":["UID\/06291\/2025"],"award-info":[{"award-number":["UID\/06291\/2025"]}]},{"award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}],"id":[{"id":"https:\/\/ror.org\/04z8k9a98","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UID\/PRR\/04539\/2025"],"award-info":[{"award-number":["UID\/PRR\/04539\/2025"]}],"id":[{"id":"https:\/\/ror.org\/04z8k9a98","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UID\/04539\/2025"],"award-info":[{"award-number":["UID\/04539\/2025"]}],"id":[{"id":"https:\/\/ror.org\/04z8k9a98","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UID\/06291\/2025"],"award-info":[{"award-number":["UID\/06291\/2025"]}],"id":[{"id":"https:\/\/ror.org\/04z8k9a98","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Marked interindividual variability in drug response remains a major challenge in clinical pharmacology and cannot be fully explained by host genetics alone. Increasing evidence indicates that the gut microbiota constitutes an additional determinant of drug efficacy and toxicity through bidirectional interactions with pharmacological therapies. This recognition has led to the emergence of pharmacomicrobiomics, a field that investigates how microbial communities influence drug disposition and response, and how drugs, in turn, alter the microbiome. Microbiome-mediated effects on drug efficacy and toxicity have been described across several therapeutic areas, including oncology, multiple sclerosis, and type 2 diabetes mellitus. Although these findings are promising, most mechanistic evidence derives from preclinical and animal studies, with relatively limited validation in controlled clinical trials. Strategies to modulate the gut microbiota, including prebiotics, probiotics, and faecal microbiota transplantation, have shown preliminary promise in optimising drug efficacy and reducing adverse effects, although methodological heterogeneity and incomplete mechanistic understanding limit their current clinical application. The identification of robust microbiome-derived biomarkers and the integration of multi-omics approaches, particularly metabolomics, are expected to accelerate the translation of pharmacomicrobiomics into precision medicine. This review summarises current evidence regarding microbiome\u2013drug interactions, the mechanisms underlying microbiome-mediated modulation of pharmacokinetics and pharmacodynamics, emerging therapeutic strategies, and the challenges that remain before pharmacomicrobiomics can be implemented in clinical practice.<\/jats:p>","DOI":"10.3390\/metabo16090602","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacomicrobiomics: From Host\u2013Microbiome\u2013Drug Interactions to Clinical Translation in Precision Medicine"],"prefix":"10.3390","volume":"16","author":[{"given":"Guilherme","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-458 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-5113","authenticated-orcid":false,"given":"Sara","family":"Domingues","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-458 Coimbra, Portugal"},{"name":"CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CiBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-8540","authenticated-orcid":false,"given":"Gabriela Jorge","family":"da Silva","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-458 Coimbra, Portugal"},{"name":"CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CiBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4277-4365","authenticated-orcid":false,"given":"Tiago","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Medical and Health Sciences, School of Health and Human Development, University of \u00c9vora, 7004-516 \u00c9vora, Portugal"},{"name":"Comprehensive Health Research Centre (CHRC), University of \u00c9vora, 7004-516 \u00c9vora, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1089\/omi.2014.0018","article-title":"Pharmacomicrobiomics: The impact of human microbiome variations on systems pharmacology and personalized therapeutics","volume":"18","author":"ElRakaiby","year":"2014","journal-title":"Omics J. Integr. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","article-title":"Mapping human microbiome drug metabolism by gut bacteria and their genes","volume":"570","author":"Zimmermann","year":"2019","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.trsl.2016.08.002","article-title":"Gut microbiome interactions with drug metabolism, efficacy, and toxicity","volume":"179","author":"Wilson","year":"2017","journal-title":"Transl. Res."},{"key":"ref_4","first-page":"375","article-title":"The impact of the gut microbiota on drug metabolism and clinical outcome","volume":"89","author":"Enright","year":"2016","journal-title":"Yale J. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nature11400","article-title":"Antibiotics in early life alter the murine colonic microbiome and adiposity","volume":"488","author":"Cho","year":"2012","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.1038\/ncomms8486","article-title":"Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment","volume":"6","author":"Nobel","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s40262-021-01032-y","article-title":"Contribution of the gut microbiome to drug disposition, pharmacokinetic and pharmacodynamic variability","volume":"60","author":"Tsunoda","year":"2021","journal-title":"Clin. Pharmacokinet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13073-016-0303-2","article-title":"Impact of the gut microbiota on inflammation, obesity, and metabolic disease","volume":"8","author":"Boulange","year":"2016","journal-title":"Genome Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1136\/gutjnl-2024-333378","article-title":"What defines a healthy gut microbiome?","volume":"73","author":"Cani","year":"2024","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lima, T., Costa, V., Nunes, C., da Silva, G.J., and Domingues, S. (2025). From dysbiosis to cardiovascular disease: The impact of gut microbiota on atherosclerosis and emerging therapies. Appl. Sci., 15.","DOI":"10.3390\/app15137084"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12967-017-1175-y","article-title":"Influence of diet on the gut microbiome and implications for human health","volume":"15","author":"Singh","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/j.apsb.2020.09.013","article-title":"The influence of the gut microbiota on the bioavailability of oral drugs","volume":"11","author":"Zhang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shi, T., Li, H., Zhang, Z., Zang, Y., Jiang, S., and Yuan, T. (2025). The effect of gut microbiome perturbation on the bioavailability of glycyrrhizic acid in rats. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17040457"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112678","DOI":"10.1016\/j.biopha.2022.112678","article-title":"The links between gut microbiota and obesity and obesity related diseases","volume":"147","author":"Geng","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., and Kim, S.W. (2015). Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137429"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G.A.D., Gasbarrini, A., and Mele, M.C. (2019). What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 7.","DOI":"10.3390\/microorganisms7010014"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00248-022-02081-x","article-title":"Human gut microbiota and drug metabolism","volume":"86","author":"Pant","year":"2023","journal-title":"Microb. Ecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature12820","article-title":"Diet rapidly and reproducibly alters the human gut microbiome","volume":"505","author":"David","year":"2014","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/0884533615609899","article-title":"Gut microbiome: What we do and don\u2019t know","volume":"30","author":"Cresci","year":"2015","journal-title":"Nutr. Clin. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13073-024-01306-7","article-title":"Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection","volume":"16","author":"Nooij","year":"2024","journal-title":"Genome Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1260","DOI":"10.1002\/mbo3.1260","article-title":"Impact of antibiotics on the human microbiome and consequences for host health","volume":"11","author":"Patangia","year":"2022","journal-title":"MicrobiologyOpen"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1017\/S0007114513002560","article-title":"Intestinal microbiota, diet and health","volume":"111","author":"Power","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41392-023-01619-w","article-title":"Drug-microbiota interactions: An emerging priority for precision medicine","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, S., Ju, D., and Zeng, X. (2024). Mechanisms and clinical implications of human gut microbiota-drug interactions in the precision medicine era. Biomedicines, 12.","DOI":"10.3390\/biomedicines12010194"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jare.2023.07.002","article-title":"Dissecting the human gut microbiome to better decipher drug liability: A once-forgotten organ takes center stage","volume":"52","author":"Cai","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114468","DOI":"10.1016\/j.biopha.2023.114468","article-title":"Exploring the potential impact of probiotic use on drug metabolism and efficacy","volume":"161","author":"Purdel","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Matuskova, Z., Anzenbacherova, E., Vecera, R., Tlaskalova-Hogenova, H., Kolar, M., and Anzenbacher, P. (2014). Administration of a probiotic can change drug pharmacokinetics: Effect of E. coli Nissle 1917 on amidarone absorption in rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087150"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.1177\/0300060518788994","article-title":"Lactobacillus plantarum IS-10506 probiotic administration increases amlodipine absorption in a rabbit model","volume":"46","author":"Saputri","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/HJH.0000000000000773","article-title":"Effects of orally administered antibiotics on the bioavailability of amlodipine: Gut microbiota-mediated drug interaction","volume":"34","author":"Yoo","year":"2016","journal-title":"J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3109\/00498258409151481","article-title":"Role of the intestinal microflora in clonazepam metabolism in the rat","volume":"14","author":"Elmer","year":"1984","journal-title":"Xenobiotica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1126\/science.1240537","article-title":"The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide","volume":"342","author":"Viaud","year":"2013","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.immuni.2016.09.009","article-title":"Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects","volume":"45","author":"Daillere","year":"2016","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1124\/jpet.111.191122","article-title":"Pharmacologic targeting of bacterial \u03b2-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice","volume":"341","author":"LoGuidice","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3109\/00498254.2013.811314","article-title":"Bacterial \u03b2-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: Mode of action and pharmacokinetics","volume":"44","author":"Saitta","year":"2014","journal-title":"Xenobiotica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1126\/science.1235872","article-title":"Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta","volume":"341","author":"Haiser","year":"2013","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.maturitas.2017.06.025","article-title":"Estrogen-gut microbiome axis: Physiological and clinical implications","volume":"103","author":"Baker","year":"2017","journal-title":"Maturitas"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.chom.2011.10.003","article-title":"Microbiome and malignancy","volume":"10","author":"Plottel","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0022-4731(80)90014-X","article-title":"In vitro metabolism of estrogens by isolated intestinal micro-organisms and by human faecal microflora","volume":"13","author":"Jarvenpaa","year":"1980","journal-title":"J. Steroid Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1126\/science.aah5043","article-title":"Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine","volume":"357","author":"Geller","year":"2017","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1126\/science.1191175","article-title":"Alleviating cancer drug toxicity by inhibiting a bacterial enzyme","volume":"330","author":"Wallace","year":"2010","journal-title":"Science"},{"key":"ref_42","first-page":"1055","article-title":"Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism","volume":"364","author":"Bess","year":"2019","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0090-9556(25)06545-6","article-title":"Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans","volume":"23","author":"Lavrijsen","year":"1995","journal-title":"Drug Metab. Dispos."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1124\/dmd.114.058354","article-title":"Gut microbiota-mediated drug interactions between lovastatin and antibiotics","volume":"42","author":"Yoo","year":"2014","journal-title":"Drug Metab. Dispos."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature15766","article-title":"Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota","volume":"528","author":"Forslund","year":"2015","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nm.4345","article-title":"Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug","volume":"23","author":"Wu","year":"2017","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1016\/0006-2952(79)90407-6","article-title":"Acetamide\u2014A metabolite of metronidazole formed by the intestinal flora","volume":"28","author":"Koch","year":"1979","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zemanova, N., Lnenickova, K., Vavreckova, M., Anzenbacherova, E., Anzenbacher, P., Zapletalova, I., Hermanova, P., Hudcovic, T., Kozakova, H., and Jourova, L. (2021). Gut microbiome affects the metabolism of metronidazole in mice through regulation of hepatic cytochromes P450 expression. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0259643"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/bdd.2244","article-title":"Effects of gut microbiota on in vivo metabolism and tissue accumulation of cytochrome P450 3A metabolized drug: Midazolam","volume":"41","author":"Togao","year":"2020","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0009-9236(98)90086-8","article-title":"Pharmacokinetics of morphine-6-glucuronide and its formation from morphine after intravenous administration","volume":"63","author":"Lotsch","year":"1998","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.1038\/s41598-018-21915-8","article-title":"Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model","volume":"8","author":"Wang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s40168-025-02142-6","article-title":"Microbiome-derived reactivation of mycophenolate explains variations in enterohepatic recirculation in kidney transplant recipients","volume":"13","author":"Drevland","year":"2025","journal-title":"Microbiome"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.aan3706","article-title":"Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors","volume":"359","author":"Routy","year":"2018","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.aan4236","article-title":"Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients","volume":"359","author":"Gopalakrishnan","year":"2018","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1136\/gut.23.12.1081","article-title":"Distribution and metabolism in healthy volunteers of disodium azodisalicylate, a potential therapeutic agent for ulcerative colitis","volume":"23","author":"Willoughby","year":"1982","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1002\/jps.24103","article-title":"On the colonic bacterial metabolism of azo-bonded prodrugsof 5-aminosalicylic acid","volume":"103","author":"Sousa","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/jps.2600840425","article-title":"Metabolism of omeprazole by gut flora in rats","volume":"84","author":"Watanabe","year":"1995","journal-title":"J. Pharm. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14728","DOI":"10.1073\/pnas.0904489106","article-title":"Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism","volume":"106","author":"Clayton","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3109\/00498257109044386","article-title":"The role of the gut flora in the metabolism of prontosil and neoprontosil in the rat","volume":"1","author":"Gingell","year":"1971","journal-title":"Xenobiotica"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2125.1998.00050.x","article-title":"Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase","volume":"46","author":"Diasio","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1248\/yakushi.122.527","article-title":"Molecular toxicological mechanism of the lethal interactions of the new antiviral drug, sorivudine, with 5-fluorouracil prodrugs and genetic deficiency of dihydropyrimidine dehydrogenase","volume":"122","author":"Watabe","year":"2002","journal-title":"Yakugaku Zasshi J. Pharm. Soc. Jpn."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/BF01299921","article-title":"Studies of two novel sulfasalazine analogs, ipsalazide and balsalazide","volume":"28","author":"Chan","year":"1983","journal-title":"Dig. Dis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Lee, J.R., Muthukumar, T., Dadhania, D., Taur, Y., Jenq, R.R., Toussaint, N.C., Ling, L., Pamer, E., and Suthanthiran, M. (2015). Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122399"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1124\/dmd.118.084772","article-title":"Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites","volume":"47","author":"Guo","year":"2019","journal-title":"Drug Metab. Dispos."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chen, W., Qian, J., Fu, J., Wu, T., Lv, M., Jiang, S., and Zhang, J. (2022). Changes in the gut microbiota may affect the clinical efficacy of oral anticoagulants. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.860237"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1097\/JS9.0000000000000673","article-title":"Exploring the complex relationship between vitamin K, gut microbiota, and warfarin variability in cardiac surgery patients","volume":"109","author":"Xue","year":"2023","journal-title":"Int. J. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1038\/s41598-021-84167-z","article-title":"Growth stimulation of Bifidobacterium from human colon using daikenchuto in an in vitro model of human intestinal microbiota","volume":"11","author":"Sasaki","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e00215","DOI":"10.1002\/prp2.215","article-title":"Daikenchuto (TU-100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K","volume":"4","author":"Hasebe","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"647","DOI":"10.2165\/00003495-199141040-00009","article-title":"Olsalazine: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease","volume":"41","author":"Wadworth","year":"1991","journal-title":"Drugs"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Elmassry, M.M., Kim, S., and Busby, B. (2021). Predicting drug-metagenome interactions: Variation in the microbial \u03b2-glucuronidase level in the human gut metagenomes. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0244876"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1124\/pr.118.015768","article-title":"Gut reactions: Breaking down xenobiotic-microbiome interactions","volume":"71","author":"Clarke","year":"2019","journal-title":"Pharmacol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Nemati, M.H., Yazdanpanah, E., Kazemi, R., Orooji, N., Dadfar, S., Oksenych, V., and Haghmorad, D. (2025). Microbiota-driven mechanisms in multiple sclerosis: Pathogenesis, therapeutic strategies, and biomarker potential. Biology, 14.","DOI":"10.3390\/biology14040435"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yu, Y., Ding, Y., Wang, S., and Jiang, L. (2025). Gut microbiota dysbiosis and its impact on Type 2 diabetes: From pathogenesis to therapeutic strategies. Metabolites, 15.","DOI":"10.3390\/metabo15060397"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1053\/j.gastro.2022.10.018","article-title":"Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy","volume":"164","author":"Chrysostomou","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Jia, L., Huang, S., Sun, B., Shang, Y., and Zhu, C. (2023). Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1149256"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1177\/0963689719873890","article-title":"The gut microbiota in multiple sclerosis: An overview of clinical trials","volume":"28","author":"Schepici","year":"2019","journal-title":"Cell Transplant."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Del Negro, I., Pez, S., Versace, S., Marziali, A., Gigli, G.L., Tereshko, Y., and Valente, M. (2023). Impact of disease-modifying therapies on gut-brain axis in multiple sclerosis. Medicina, 60.","DOI":"10.3390\/medicina60010006"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ferri, C., Castellazzi, M., Merli, N., Laudisi, M., Baldin, E., Baldi, E., Mancabelli, L., Ventura, M., and Pugliatti, M. (2023). Gut microbiota changes during dimethyl fumarate treatment in patients with multiple sclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032720"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1136\/gutjnl-2021-326264","article-title":"Cancer pharmacomicrobiomics: Targeting microbiota to optimise cancer therapy outcomes","volume":"71","author":"Ting","year":"2022","journal-title":"Gut"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e22350","DOI":"10.1096\/fj.202101986R","article-title":"Pharmacomicrobiomics: Influence of gut microbiota on drug and xenobiotic metabolism","volume":"36","author":"Dikeocha","year":"2022","journal-title":"FASEB J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.copbio.2015.09.001","article-title":"Prebiotics: Why definitions matter","volume":"37","author":"Hutkins","year":"2016","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S156","DOI":"10.1097\/MCG.0b013e31817f184e","article-title":"FAO Technical meeting on prebiotics","volume":"42","author":"Pineiro","year":"2008","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114510003363","article-title":"Prebiotic effects: Metabolic and health benefits","volume":"104","author":"Roberfroid","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3945\/an.115.010587","article-title":"Can we prevent obesity-related metabolic diseases by dietary modulation of the gut microbiota?","volume":"7","author":"Brahe","year":"2016","journal-title":"Adv. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1139\/y03-107","article-title":"Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2","volume":"81","author":"Brubaker","year":"2003","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Conti, G., D\u2019Amico, F., Fabbrini, M., Brigidi, P., Barone, M., and Turroni, S. (2022). Pharmacomicrobiomics in anticancer therapies: Why the gut microbiota should be pointed out. Genes, 14.","DOI":"10.3390\/genes14010055"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_88","unstructured":"Food and Agriculture Organization of the United Nations (2006). Probiotics in Food: Health and Nutritional Properties and Guidelines for Evaluation, Food and Agriculture Organization of the United Nations."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.nut.2017.06.024","article-title":"Probiotics and gastrointestinal conditions: An overview of evidence from the Cochrane Collaboration","volume":"45","author":"Parker","year":"2018","journal-title":"Nutrition"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00253-021-11646-8","article-title":"Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics","volume":"106","author":"Yadav","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"791","DOI":"10.3109\/00498254.2012.660508","article-title":"The influence of probiotic treatment on sulfasalazine metabolism in rat","volume":"42","author":"Lee","year":"2012","journal-title":"Xenobiotica"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1756-185X.2009.01449.x","article-title":"The effects of an orally administered probiotic on sulfasalazine metabolism in individuals with rheumatoid arthritis: A preliminary study","volume":"13","author":"Lee","year":"2010","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Li, B., Kwok, L.Y., Wang, D., Li, L., Guo, S., and Chen, Y. (2023). Integrating metabolomics, bionics, and culturomics to study probiotics-driven drug metabolism. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1047863"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/BF03191026","article-title":"Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats","volume":"33","author":"Butt","year":"2008","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0140-6736(19)31266-8","article-title":"The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications","volume":"394","author":"Allegretti","year":"2019","journal-title":"Lancet"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1136\/gutjnl-2016-313017","article-title":"European consensus conference on faecal microbiota transplantation in clinical practice","volume":"66","author":"Cammarota","year":"2017","journal-title":"Gut"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"257","DOI":"10.5946\/ce.2015.117","article-title":"Fecal microbiota transplantation: Current applications, effectiveness, and future perspectives","volume":"49","author":"Choi","year":"2016","journal-title":"Clin. Endosc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.gtc.2016.09.012","article-title":"Fecal microbiota transplantation","volume":"46","author":"Vindigni","year":"2017","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/j.cell.2020.05.001","article-title":"Personalized mapping of drug metabolism by the human gut microbiome","volume":"181","author":"Javdan","year":"2020","journal-title":"Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40793-022-00444-y","article-title":"Microbiome ethics, guiding principles for microbiome research, use and knowledge management","volume":"17","author":"Lange","year":"2022","journal-title":"Environ. Microbiome"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10669-024-09965-y","article-title":"Can societal and ethical implications of precision microbiome engineering be applied to the built environment? A systematic review of the literature","volume":"44","author":"Hardwick","year":"2024","journal-title":"Environ. Syst. Decis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41398-024-03208-z","article-title":"The role of gut microbiota and metabolomic pathways in modulating the efficacy of SSRIs for major depressive disorder","volume":"14","author":"Jiang","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2361491","DOI":"10.1080\/19490976.2024.2361491","article-title":"Gut microbiome encoded purine and amino acid pathways present prospective biomarkers for predicting metformin therapy efficacy in newly diagnosed T2D patients","volume":"16","author":"Elbere","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.ebiom.2019.05.009","article-title":"Bringing microbiome-drug interaction research into the clinic","volume":"44","author":"Guthrie","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_105","unstructured":"Singh, S.K., Vamanu, E., Rai, S.N., and Singh, A.K. (2025). Strategies for Biomarker Identification and Validation in Precision Medicine: Microbial Predictors, Data Integration, Machine Learning, and Clinical Trial Insights. Microbiota Profiling for Precision Medicine: Biomarker-Targeted Drug Delivery Strategies, Springer Nature."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/9\/602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:11:34Z","timestamp":1787573494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/9\/602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,23]]},"references-count":105,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["metabo16090602"],"URL":"https:\/\/doi.org\/10.3390\/metabo16090602","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,23]]}}}