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Despite living symbiotically with the human body, the gut microbiome is represented as potential drug targets because of its ability to modify the pharmacokinetics of orally administered drugs. Structural biology analysis indicates the existence of homology between transport proteins of microbial cells and membranes of enterocytes. It is speculated that structural similarity in the protein transporters may provoke an unwanted phenomenon of drug uptake by the gut microbiome present in the small intestine of the host. Considering this hypothesis, we analyzed the absorbance of orally administered caffeine by the gut microbiota in in vivo albino rat model through the RP-HPLC-UV approach. Microbiome absorbed the caffeine maximally at 2\u00a0hours and minimally at 5\u00a0hours post-drug administration following first-order absorption kinetics in a nonlinear way. Drug absorbance of microbial pellet and percent dose recovery was found significantly higher ( P \u2264 .05) at 2\u00a0hours post-administration as compared to all other groups. As speculated, our findings advocated the phenomenon that the gut microbiome influences the absorption of caffeine molecules. Members of the gut microbiome exhibited grouped behavior following first-order absorption kinetics in a nonlinear pattern.<\/jats:p>","DOI":"10.1177\/15593258211033111","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T13:39:01Z","timestamp":1629207541000},"page":"155932582110331","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["The Competitive Absorption by the Gut Microbiome Suggests the First-Order Absorption Kinetics of Caffeine"],"prefix":"10.1177","volume":"19","author":[{"given":"Imran","family":"Mukhtar","sequence":"first","affiliation":[{"name":"Department of Physiology, Government College University, Faisalabad, Pakistan"},{"name":"Sir Sadiq Muhammad Khan Abbasi Post Graduate Medical College, Faculty of Medicine and Allied Health Sciences, The Islamia University of Bahawalpur, Bahawalpur, 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