{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:23Z","timestamp":1790575043142,"version":"4.1.0"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Gut microbiota plays an important role in metabolising environmental chemicals and drugs. It affects the susceptibility of the host to toxicity by modifying metabolism, which can be captured by\n                    <jats:italic>in-vitro<\/jats:italic>\n                    assays and translated using\n                    <jats:italic>in silico<\/jats:italic>\n                    models.\n                    <jats:italic>In-silico<\/jats:italic>\n                    models like physiologically based pharmacokinetic (PBPK) models can predict the concentration-time profile of compounds across different tissues and organs. Despite the recognized importance of gut microbiota in shaping absorption, distribution, metabolism and excretion (ADME) profiles for a wide range of compounds, PBPK models do not include gut microbiota either due to the unavailability of data or to reduce model complexity. This inclusion becomes of utmost importance when metabolism by gut microbiota shape the ADME profile. In this review, we outline the key strategies and considerations for integrating gut microbiota into PBPK models as part of New Approach Methodologies (NAMs), covering the essential equations, parameterization approaches, and\n                    <jats:italic>in-vitro<\/jats:italic>\n                    -to-\n                    <jats:italic>in-vivo<\/jats:italic>\n                    extrapolation (IVIVE) methods required for model development and validation. We also focus on the limitations of the IVIVE methodologies including population-level variability modelling, and the emerging application of machine learning for microbial parameter inference. We further discuss extended compartmentalization, as well as the integration of genome-scale metabolic (GSM) network models to capture microbial pathway diversity. The review also highlights the broad applications of microbiota-based PBPK models, including personalized medicine, translational modelling, compound-microbiota interactions, and the compound-microbiota-diet axis. Additionally, we examine the current regulatory landscape, identifying existing gaps in PBPK guidelines with respect to microbial metabolism, and propose directions for developing harmonized reporting frameworks. Finally, we discuss future directions including multi-omics integration, bidirectional gut-liver signalling. Together, this review provides a practical roadmap for building microbiota-informed PBPK models that improve kinetic predictions and advance personalized risk assessment.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1840947","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:45:30Z","timestamp":1790574330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiota-based PBPK model: new approach methodology for assessing the kinetics of drugs and chemicals"],"prefix":"10.3389","volume":"17","author":[{"given":"Deepika","family":"Deepika","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Institut de Recerca Biom\u00e8dica Catalunya Sud (IRBCatSud), Universitat Rovira i Virgili (URV)","place":["Tarragona, Spain"]},{"name":"Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanchan","family":"Bharti","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Institut de Recerca Biom\u00e8dica Catalunya Sud (IRBCatSud), Universitat Rovira i Virgili (URV)","place":["Tarragona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Biosca Brull","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili","place":["Tarragona, Spain"]},{"name":"Institut de Recerca Biom\u00e8dica Catalunya Sud, Center of Environmental, Food and Toxicological Technology (TECNATOX), Universitat Rovira i Virgili","place":["Reus, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Sabuz","sequence":"additional","affiliation":[{"name":"Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yemurai","family":"Musengi","sequence":"additional","affiliation":[{"name":"Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Institut de Recerca Biom\u00e8dica Catalunya Sud (IRBCatSud), Universitat Rovira i Virgili (URV)","place":["Tarragona, Spain"]},{"name":"Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1080\/15287390802328630","article-title":"Splenda alters gut microflora and increases intestinal P-Glycoprotein and cytochrome P-450 in Male rats","volume":"71","author":"Abou-Donia","year":"2008","journal-title":"J. Toxicol. Environ. Health, Part A"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4942","DOI":"10.3390\/ijms25094942","article-title":"The mediterranean diet, its microbiome connections, and cardiovascular health: a narrative review","volume":"25","author":"Abrignani","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3390\/metabo14030155","article-title":"Pesticides: unintended impact on the hidden world of gut microbiota","volume":"14","author":"Ali","year":"2024","journal-title":"Metabolites"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1007\/s40262-022-01169-4","article-title":"Altered bioavailability and pharmacokinetics in Crohn\u2019s disease: capturing systems parameters for PBPK to assist with predicting the fate of orally administered drugs","volume":"61","author":"Alrubia","year":"2022","journal-title":"Clin. Pharmacokinet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41540-025-00631-w","article-title":"SIMBA-GNN: mechanistic graph learning for microbiome prediction","volume":"12","author":"Aminian-Dehkordi","year":"2025","journal-title":"Npj Syst. Biol. Appl."},{"key":"B6","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1039\/D3MO00089C","article-title":"Integrated multi-omics analyses of microbial communities: a review of the current state and future directions","volume":"19","author":"Ar\u0131kan","year":"2023","journal-title":"Mol. Omics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.3390\/ijerph19031368","article-title":"Impact of contaminants on microbiota: linking the gut\u2013brain axis with neurotoxicity","volume":"19","author":"Balaguer-Trias","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B8","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3390\/foods12020270","article-title":"The impact of ellagitannins and their metabolites through gut microbiome on the gut health and brain wellness within the gut\u2013brain axis","volume":"12","author":"Banc","year":"2023","journal-title":"Foods"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/nu17010002","article-title":"Ultra-processed food and gut microbiota: do additives affect eubiosis? A narrative review","volume":"17","author":"Bevilacqua","year":"2024","journal-title":"Nutrients"},{"key":"B10","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3389\/fphys.2017.00487","article-title":"Gut microbiome response to sucralose and its potential role in inducing liver inflammation in mice","volume":"8","author":"Bian","year":"2017","journal-title":"Front. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1124\/dmd.118.083402","article-title":"How to determine the role of the microbiome in drug disposition","volume":"46","author":"Bisanz","year":"2018","journal-title":"Drug Metabol. Dispos."},{"key":"B12","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/s41596-018-0119-1","article-title":"INFOGEST static in vitro simulation of gastrointestinal food digestion","volume":"14","author":"Brodkorb","year":"2019","journal-title":"Nat. Protoc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.2337\/db07-1403","article-title":"Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet\u2013induced obesity and diabetes in mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"B14","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/nature14232","article-title":"Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome","volume":"519","author":"Chassaing","year":"2015","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"742394","DOI":"10.3389\/fmed.2021.742394","article-title":"Pharmacomicrobiomics: exploiting the drug-microbiota interactions in antihypertensive treatment","volume":"8","author":"Chen","year":"2022","journal-title":"Front. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s42003-024-06330-2","article-title":"Mitigating gut microbial degradation of levodopa and enhancing brain dopamine: implications in Parkinson\u2019s disease","volume":"7","author":"Cheng","year":"2024","journal-title":"Commun. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e70246","DOI":"10.1002\/psp4.70246","article-title":"Translational modeling of gut microbiome-mediated drug metabolism: a case example of sulfasalazine","volume":"15","author":"Cheng","year":"2026","journal-title":"CPT Pharmacometrics and Syst. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1016\/j.csbj.2025.03.016","article-title":"Computational analysis of the gut microbiota-mediated drug metabolism","volume":"27","author":"Chum","year":"2025","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"16003","DOI":"10.1038\/npjbiofilms.2016.3","article-title":"The gut microbiota: a major player in the toxicity of environmental pollutants?","volume":"2","author":"Claus","year":"2016","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41540-018-0048-1","article-title":"Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation","volume":"4","author":"Cordes","year":"2018","journal-title":"NPJ Syst. Biol. Appl."},{"key":"B21","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/ecco-jcc\/jjaa143","article-title":"Gut microbiota-driven drug metabolism in inflammatory bowel disease","volume":"15","author":"Crouwel","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2337\/dc16-1324","article-title":"Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid\u2013producing microbiota in the gut","volume":"40","author":"Cuesta-Zuluaga","year":"2017","journal-title":"Diabetes Care"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3473","DOI":"10.3390\/ijerph20043473","article-title":"The role of \u2018Physiologically Based Pharmacokinetic Model (PBPK)\u2019 new approach methodology (NAM) in pharmaceuticals and environmental chemical risk assessment","volume":"20","author":"Deepika","year":"2023","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B24","doi-asserted-by":"publisher","first-page":"114074","DOI":"10.1016\/j.envres.2022.114074","article-title":"Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model","volume":"215","author":"Deepika","year":"2022","journal-title":"Environ. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3757","DOI":"10.3390\/nu16213757","article-title":"Mitigating dietary bisphenol exposure through the gut microbiota: the role of next-generation probiotics in bacterial detoxification","volume":"16","author":"Emanowicz","year":"2024","journal-title":"Nutrients"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1093\/bioinformatics\/btw107","article-title":"An algorithm for designing minimal microbial communities with desired metabolic capacities","volume":"32","author":"Eng","year":"2016","journal-title":"Bioinformatics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1021\/acs.molpharmaceut.6b01155","article-title":"Impact of gut microbiota-mediated bile acid metabolism on the solubilization capacity of bile salt micelles and drug solubility","volume":"14","author":"Enright","year":"2017","journal-title":"Mol. Pharm."},{"key":"B28","unstructured":"Guideline on the reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation\n          \n          \n          2018"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e0142793","DOI":"10.1371\/journal.pone.0142793","article-title":"\u201cDesign and Investigation of PolyFermS in vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon\u201d ed. Tiffany L. Weir","volume":"10","author":"Fehlbaum","year":"2015","journal-title":"PLoS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1080\/19490976.2017.1334033","article-title":"Fecal microbiota variation across the lifespan of the healthy laboratory rat","volume":"8","author":"Flemer","year":"2017","journal-title":"Gut Microbes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrgastro.2012.156","article-title":"The role of the gut microbiota in nutrition and health","volume":"9","author":"Flint","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.3390\/nu12041158","article-title":"Endocrine disruptors in food: impact on gut microbiota and metabolic diseases","volume":"12","author":"G\u00e1lvez-Ontiveros","year":"2020","journal-title":"Nutrients"},{"key":"B33","doi-asserted-by":"publisher","first-page":"5281","DOI":"10.1007\/s00203-021-02516-y","article-title":"Structural diversity, functional aspects and future therapeutic applications of human gut microbiome","volume":"203","author":"Ghosh","year":"2021","journal-title":"Archives Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.3390\/jcm15031210","article-title":"From population-based PBPK to individualized virtual twins: clinical validation and applications in medicine","volume":"15","author":"Gon\u00e7alves","year":"2026","journal-title":"J. Clin. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"16013","DOI":"10.1038\/npjsba.2016.13","article-title":"Model-based dietary optimization for late-stage, levodopa-treated, Parkinson\u2019s disease patients","volume":"2","author":"Guebila","year":"2016","journal-title":"NPJ Syst. Biol. Appl."},{"key":"B36","doi-asserted-by":"publisher","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":"B37","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4161\/gmic.27915","article-title":"Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics","volume":"5","author":"Haiser","year":"2014","journal-title":"Gut Microbes"},{"key":"B38","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s10928-016-9492-y","article-title":"Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine","volume":"43","author":"Hartmanshenn","year":"2016","journal-title":"J. Pharmacokinet. Pharmacodynamics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"100346","DOI":"10.1016\/j.coisb.2021.05.007","article-title":"Advances in constraint-based modelling of microbial communities","volume":"27","author":"Heinken","year":"2021","journal-title":"Curr. Opin. Syst. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"118910","DOI":"10.1016\/j.ecoenv.2025.118910","article-title":"The influence of polycyclic aromatic hydrocarbons exposure on the gut microbiome composition and inflammatory responses","volume":"303","author":"Jeong","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B41","doi-asserted-by":"publisher","first-page":"01303","DOI":"10.3389\/fphar.2020.01303","article-title":"Gut microbiome alters the activity of liver cytochromes P450 in mice with sex-dependent differences","volume":"11","author":"Jourov\u00e1","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1124\/dmd.115.063867","article-title":"Gut microbiota-mediated drug-antibiotic interactions","volume":"43","author":"Kim","year":"2015","journal-title":"Drug Metabolism Dispos."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1271\/bbb.130404","article-title":"Transport mechanisms for soy isoflavones and microbial metabolites dihydrogenistein and dihydrodaidzein across monolayers and membranes","volume":"77","author":"Kobayashi","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"eaag2770","DOI":"10.1126\/science.aag2770","article-title":"Chemical transformation of xenobiotics by the human gut microbiota","volume":"356","author":"Koppel","year":"2017","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1021\/acs.molpharmaceut.2c00224","article-title":"Usefulness of optimized human fecal material in simulating the bacterial degradation of sulindac and sulfinpyrazone in the lower intestine","volume":"19","author":"Kostantini","year":"2022","journal-title":"Mol. Pharm."},{"key":"B46","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1002\/psp4.12134","article-title":"Applied concepts in PBPK modeling: how to build a PBPK\/PD model","volume":"5","author":"Kuepfer","year":"2016","journal-title":"CPT Pharmacometrics and Syst. Pharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/psp4.12901","article-title":"Predicting changes in the pharmacokinetics of CYP3A\u2010metabolized drugs in hepatic impairment and insights into factors driving these changes","volume":"12","author":"Ladumor","year":"2023","journal-title":"CPT Pharmacometrics and Syst. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"100106","DOI":"10.1016\/j.medmic.2024.100106","article-title":"Antibiotics and the gut microbiome: understanding the impact on human health","volume":"20","author":"Lathakumari","year":"2024","journal-title":"Med. Microecol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e202500022","DOI":"10.1002\/aisy.202500022","article-title":"AI-driven microphysiological systems for advancing nanoparticle therapeutics","volume":"7","author":"Lee","year":"2025","journal-title":"Adv. Intell. Syst."},{"key":"B50","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1517\/17425255.2016.1121234","article-title":"The influence of gut microbiota on drug metabolism and toxicity","volume":"12","author":"Li","year":"2016","journal-title":"Expert Opin. Drug Metabol. and Toxicol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"105171","DOI":"10.1016\/j.tiv.2021.105171","article-title":"Next generation risk assessment (NGRA): bridging in vitro points-of-departure to human safety assessment using physiologically-based kinetic (PBK) modelling \u2013 a case study of doxorubicin with dose metrics considerations","volume":"74","author":"Li","year":"2021","journal-title":"Toxicol. Vitro"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e26991","DOI":"10.1016\/j.heliyon.2024.e26991","article-title":"Short-chain fatty acids in nonalcoholic fatty liver disease: new prospects for short-chain fatty acids as therapeutic targets","volume":"10","author":"Li","year":"2024","journal-title":"Heliyon"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1007\/s11095-024-03725-y","article-title":"A combination of machine learning and PBPK modeling approach for pharmacokinetics prediction of small molecules in humans","volume":"41","author":"Li","year":"2024","journal-title":"Pharm. Res."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1101\/2023.06.22.546161","article-title":"Genome-scale metabolic model predicts mechanistic differences in metabolic gradient of spatially resolved small intestine villi","author":"Lim","year":"2023"},{"key":"B55","doi-asserted-by":"publisher","first-page":"471","DOI":"10.14573\/altex.2210031","article-title":"Development of physiologically based gut absorption model for probabilistic prediction of environmental chemical bioavailability","volume":"40","author":"Lin","year":"2023","journal-title":"ALTEX."},{"key":"B56","doi-asserted-by":"publisher","first-page":"113623","DOI":"10.1016\/j.ecoenv.2022.113623","article-title":"Effects of bisphenol A on reproductive toxicity and gut microbiota dysbiosis in Male rats","volume":"239","author":"Liu","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1098386","DOI":"10.3389\/fmicb.2023.1098386","article-title":"Role of gut microbiota in infectious and inflammatory diseases","volume":"14","author":"Maciel-Fiuza","year":"2023","journal-title":"Front. Microbiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12866-023-02791-3","article-title":"Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate irinotecan-associated toxicity","volume":"23","author":"Mahdy","year":"2023","journal-title":"BMC Microbiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1254073","DOI":"10.3389\/fmicb.2023.1254073","article-title":"Application of artificial intelligence approaches to predict the metabolism of xenobiotic molecules by human gut microbiome","volume":"14","author":"Malwe","year":"2023","journal-title":"Front. Microbiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"110609","DOI":"10.1016\/j.nut.2019.110609","article-title":"Effect of ultra-processed diet on gut microbiota and thus its role in neurodegenerative diseases","volume":"71","author":"Mart\u00ednez Leo","year":"2020","journal-title":"Nutrition"},{"key":"B61","doi-asserted-by":"publisher","first-page":"e87150","DOI":"10.1371\/journal.pone.0087150","article-title":"Administration of a probiotic can change drug pharmacokinetics: effect of E. coli nissle 1917 on amidarone absorption in rats","volume":"9","author":"Matuskova","year":"2014","journal-title":"PLoS One"},{"key":"B62","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41579-023-00969-0","article-title":"The gut microbiota and its biogeography","volume":"22","author":"McCallum","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.toxrep.2020.07.010","article-title":"An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone","volume":"7","author":"Mendez-Catala","year":"2020","journal-title":"Toxicol. Rep."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2100443","DOI":"10.1002\/mnfr.202100443","article-title":"PBK model-based prediction of intestinal microbial and host metabolism of zearalenone and consequences for its estrogenicity","volume":"65","author":"Mendez-Catala","year":"2021","journal-title":"Mol. Nutr. and Food Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s40263-024-01073-4","article-title":"The gut microbiota in parkinson disease: interactions with drugs and potential for therapeutic applications","volume":"38","author":"Menozzi","year":"2024","journal-title":"CNS Drugs"},{"key":"B66","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1038\/s41467-024-46888-3","article-title":"Multi-omic integration of microbiome data for identifying disease-associated modules","volume":"15","author":"Muller","year":"2024","journal-title":"Nat. Commun."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.3389\/fmicb.2018.02897","article-title":"Comparative microbiome signatures and short-chain fatty acids in mouse, rat, non-human primate, and human feces","volume":"9","author":"Nagpal","year":"2018","journal-title":"Front. Microbiol."},{"key":"B68","volume-title":"Guidance Document on the Characterisation, Validation and Reporting of Physiologically Based Kinetic (PBK) Models for Regulatory Purposes OECD Series on Testing and Assessment","year":"2021"},{"key":"B69","doi-asserted-by":"publisher","first-page":"6281","DOI":"10.1021\/jf0509714","article-title":"Activation of proestrogens from hops (Humulus Lupulus L.) by intestinal microbiota; conversion of isoxanthohumol into 8-Prenylnaringenin","volume":"53","author":"Possemiers","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1093\/jn\/136.7.1862","article-title":"The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-Prenylnaringenin in vitro and in the human intestine","volume":"136","author":"Possemiers","year":"2006","journal-title":"J. Nutr."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1371312","DOI":"10.3389\/fcimb.2024.1371312","article-title":"Microbiota, natural products, and human health: exploring interactions for therapeutic insights","volume":"14","author":"Qadri","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/s41564-025-01972-2","article-title":"Moving from genome-scale to community-scale metabolic models for the human gut microbiome","volume":"10","author":"Quinn-Bohmann","year":"2025","journal-title":"Nat. Microbiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"16163","DOI":"10.1021\/acs.jafc.4c00969","article-title":"Physiologically based kinetic modeling-facilitated quantitative in vitro to in vivo extrapolation to predict the effects of aloe-emodin in rats and humans","volume":"72","author":"Ren","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"B74","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.neuro.2019.08.010","article-title":"The role of the gut microbiome in mediating neurotoxic outcomes to PCB exposure","volume":"75","author":"Rude","year":"2019","journal-title":"NeuroToxicol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0304-4165(02)00418-X","article-title":"Excretion of bisphenol A-glucuronide into the small intestine and deconjugation in the cecum of the rat","volume":"1573","author":"Sakamoto","year":"2002","journal-title":"Biochimica Biophysica Acta (BBA) - General Subj."},{"key":"B76","doi-asserted-by":"publisher","first-page":"e1002533","DOI":"10.1101\/036103","article-title":"Revised estimates for the number of human and bacteria cells in the body","volume":"14","author":"Sender","year":"2016","journal-title":"PLoS Biol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1355S","DOI":"10.3945\/jn.109.119776","article-title":"Equol: history, chemistry, and formation","volume":"140","author":"Setchell","year":"2010","journal-title":"J. Nutr."},{"key":"B78","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2165\/00003088-200948030-00001","article-title":"Sex differences in pharmacokinetics and pharmacodynamics","volume":"48","author":"Soldin","year":"2009","journal-title":"Clin. Pharmacokinet."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2008.07.009","article-title":"The gastrointestinal microbiota as a site for the biotransformation of drugs","volume":"363","author":"Sousa","year":"2008","journal-title":"Int. J. Pharm."},{"key":"B80","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.toxlet.2024.04.013","article-title":"Physiologically based kinetic (PBK) modeling as a new approach methodology (NAM) for predicting systemic levels of gut microbial metabolites","volume":"396","author":"Stevanoska","year":"2024","journal-title":"Toxicol. Lett."},{"key":"B81","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.cmet.2019.06.009","article-title":"Bacterial metabolism and antibiotic efficacy","volume":"30","author":"Stokes","year":"2019","journal-title":"Cell Metab."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1023\/A:1020483911355","article-title":"Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs","volume":"19","author":"Sun","year":"2002","journal-title":"Pharm. Res."},{"key":"B83","doi-asserted-by":"publisher","first-page":"109946","DOI":"10.1016\/j.cbi.2022.109946","article-title":"Development of a physiologically based pharmacokinetic model to predict Irinotecan disposition during inflammation","volume":"360","author":"Tao","year":"2022","journal-title":"Chemico-Biological Interact."},{"key":"B84","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.coisb.2017.06.001","article-title":"Quantitative systems pharmacology and the personalized drug\u2013microbiota\u2013diet axis","volume":"4","author":"Thiele","year":"2017","journal-title":"Curr. Opin. Syst. Biol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1500901","DOI":"10.1002\/mnfr.201500901","article-title":"Urolithins, the rescue of \u2018Old\u2019 Metabolites to Understand a \u2018New\u2019 concept: metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status","volume":"61","author":"Tom\u00e1s-Barber\u00e1n","year":"2017","journal-title":"Mol. Nutr. and Food Res."},{"key":"B86","unstructured":"New approach methods (NAMs)\n          \n          \n          2024"},{"key":"B87","unstructured":"Physiologically based pharmacokinetic analyses\u2014format and content guidance for industry\n          \n          \n          2018"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.2903\/sp.efsa.2024.EN-8826","article-title":"Review of new approach methodologies for application in risk assessment of nanoparticles in the food and feed sector: status and challenges","volume":"21","author":"Usmani","year":"2024","journal-title":"EFSA Support. Publ."},{"key":"B89","doi-asserted-by":"publisher","first-page":"eadg8357","DOI":"10.1126\/scitranslmed.adg8357","article-title":"Integrating the gut microbiome and pharmacology","volume":"16","author":"Verdegaal","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"B90","doi-asserted-by":"publisher","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":"B91","doi-asserted-by":"publisher","first-page":"691304","DOI":"10.3389\/fimmu.2021.691304","article-title":"Abnormalities in gut microbiota and metabolism in patients with chronic spontaneous urticaria","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1021\/acs.jafc.1c03950","article-title":"Use of physiologically based pharmacokinetic modeling to predict human gut microbial conversion of daidzein to S-Equol","volume":"70","author":"Wang","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"B93","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1002\/jcsm.13037","article-title":"Population-based metagenomics analysis reveals altered gut microbiome in sarcopenia: data from the Xiangya sarcopenia study","volume":"13","author":"Wang","year":"2022","journal-title":"J. Cachexia, Sarcopenia Muscle"},{"key":"B94","doi-asserted-by":"publisher","first-page":"234","DOI":"10.4161\/gmic.19934","article-title":"Comparative evaluation of establishing a human gut microbial community within rodent models","volume":"3","author":"Wos-Oxley","year":"2012","journal-title":"Gut Microbes"},{"key":"B95","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1136\/gutjnl-2014-308209","article-title":"Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production","volume":"65","author":"Wu","year":"2016","journal-title":"Gut"},{"key":"B96","doi-asserted-by":"publisher","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":"B97","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1159\/000447690","article-title":"Association of intestinal microbiota with metabolic markers and dietary habits in patients with type 2 diabetes","volume":"94","author":"Yamaguchi","year":"2016","journal-title":"Digestion"},{"key":"B98","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.taap.2015.10.016","article-title":"Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A","volume":"289","author":"Yang","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1521068","DOI":"10.3389\/fphar.2025.1521068","article-title":"High-performance PBPK model for predicting CYP3A4 induction-mediated drug interactions: a refined and validated approach","volume":"16","author":"Yang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13578-025-01385-y","article-title":"Distribution of gut microbiota across intestinal segments and their impact on human physiological and pathological processes","volume":"15","author":"Yang","year":"2025","journal-title":"Cell and Biosci."},{"key":"B101","doi-asserted-by":"publisher","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 Metabolism Dispos."},{"key":"B102","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13568-019-0790-9","article-title":"Evaluation of the effects of four media on human intestinal microbiota culture in vitro","volume":"9","author":"Yousi","year":"2019","journal-title":"Amb. Express"},{"key":"B103","doi-asserted-by":"publisher","first-page":"152365","DOI":"10.1016\/j.tox.2020.152365","article-title":"Perfluorooctane sulfonate alters gut microbiota-host metabolic homeostasis in mice","volume":"431","author":"Zhang","year":"2020","journal-title":"Toxicology"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1007\/s00204-024-03936-7","article-title":"Application of physiologically based (PBK) modeling to quantify the effect of the antibiotic tobramycin on bile acid levels in human plasma","volume":"99","author":"Zhang","year":"2025","journal-title":"Archives Toxicol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"1301468","DOI":"10.3389\/fnut.2023.1301468","article-title":"The interaction between ginseng and gut microbiota","volume":"10","author":"Zhao","year":"2023","journal-title":"Front. Nutr."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1046910","DOI":"10.3389\/fneur.2023.1046910","article-title":"A review of studies on gut microbiota and levodopa metabolism","volume":"14","author":"Zhong","year":"2023","journal-title":"Front. Neurol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"100021","DOI":"10.1016\/j.engmic.2022.100021","article-title":"Genome-scale metabolic modeling in antimicrobial pharmacology","volume":"2","author":"Zhu","year":"2022","journal-title":"Eng. Microbiol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"731288","DOI":"10.3389\/fphar.2021.731288","article-title":"Gut microbiota: novel therapeutic target of ginsenosides for the treatment of obesity and its complications","volume":"12","author":"Zhuang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B109","doi-asserted-by":"publisher","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":"B110","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1080\/19490976.2019.1667724","article-title":"Insights from pharmacokinetic models of host-microbiome drug metabolism","volume":"11","author":"Zimmermann-Kogadeeva","year":"2020","journal-title":"Gut Microbes"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1840947\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:45:32Z","timestamp":1790574332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1840947\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":110,"alternative-id":["10.3389\/fphar.2026.1840947"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1840947","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"article-number":"1840947"}}