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Such strategies require comprehensive, individualized assessment of microbial ecosystems and their functional responses, an objective that remains difficult to achieve in vivo. In vitro gut models offer a promising alternative, maintaining personalized microbial communities in controlled environments and enabling detailed investigation of microbiome dynamics. Complementary microbe\u2013host co-culture systems incorporating human cells further permit mechanistic interrogation of host responses to microbial stimuli. Together, these integrated platforms offer a translational framework for developing tailored therapeutics. In this Perspective, we examine how in vitro gut models can advance microbiome-based personalized medicine, discuss key determinants of therapeutic variability, and outline the relevance, limitations, and future directions of these systems in designing targeted, more effective interventions.<\/jats:p>","DOI":"10.1093\/femsre\/fuag038","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:19:32Z","timestamp":1785755972000},"source":"Crossref","is-referenced-by-count":0,"title":["Precision microbiome medicine and therapeutics: the enabling role of\n                    <i>in vitro<\/i>\n                    gut models"],"prefix":"10.1093","volume":"50","author":[{"given":"Zhan","family":"Huang","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Centre de Recherche Saint-Antoine, CRSA , F-75012 Paris ,","place":["France"]},{"name":"Gut, Liver & Microbiome Research (GLIMMER) FHU , F-75012 Paris ,","place":["France"]},{"name":"Microbiota I-Center (MagIC) , Hong Kong SAR ,","place":["China"]},{"name":"State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong Department of Medicine and Therapeutics, , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew C","family":"Ng","sequence":"additional","affiliation":[{"name":"Microbiota I-Center (MagIC) , Hong Kong SAR ,","place":["China"]},{"name":"State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong Department of Medicine and Therapeutics, , Hong Kong ,","place":["China"]},{"name":"New Cornerstone Science Laboratory, The Chinese University of Hong Kong , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Sokol","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Centre de Recherche Saint-Antoine, CRSA , F-75012 Paris ,","place":["France"]},{"name":"Gut, Liver & Microbiome Research (GLIMMER) FHU , F-75012 Paris ,","place":["France"]},{"name":"Sorbonne Universit\u00e9 Department of Gastroenterology, , AP-HP, H\u00f4pital Saint Antoine, F-75012 Paris ,","place":["France"]},{"name":"INRAE UMR1319 Micalis, AgroParisTech , F-78322 Jouy-en-Josas ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2946-4808","authenticated-orcid":false,"given":"Nathalie","family":"Rolhion","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Centre de Recherche Saint-Antoine, CRSA , F-75012 Paris ,","place":["France"]},{"name":"Gut, Liver & Microbiome Research (GLIMMER) FHU , F-75012 Paris 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