Population-level Metagenomics Uncovers Distinct Effects of Multiple Medications on the Human Gut Microbiome

• DOI: 10.1053/j.gastro.2022.06.070
• Publication Date: 2022-07-02T00:52:33Z
• Authors: Naoyoshi Nagata; Suguru Nishijima; Tohru Miyoshi-Aki...; Yasushi Kojima; Moto Kimura; Ryo Aoki; Mitsuru Ohsugi; Kohjiro Ueki; Kuniko Miki; Eri Iwata; Kayoko Hayakawa; Norio Ohmagari; Shinichi Oka; Masashi Mizokami; Takao Itoi; Takashi Kawai; Naomi Uemura; Masahira Hattori
• Keywords: Gut microbiome

Background & aimsMedication is a major determinant of human gut microbiome structure, and its overuse increases the risks morbidity mortality. However, effects certain commonly prescribed drugs multiple medications on are still underinvestigated.MethodsWe performed shotgun metagenomic analysis fecal samples from 4198 individuals in Japanese 4D (Disease, Drug, Diet, Daily life) project. A total 759 were profiled, other metadata, such as anthropometrics, lifestyles, diets, physical activities, diseases, prospectively collected. Second collected 243 to assess drug initiation discontinuation microbiome.ResultsWe found that numerous across different treatment categories influence microbiome; more than 70% we profiled had not been examined before. Individuals exposed drugs, polypharmacy, showed distinct structures harboring significantly abundant upper gastrointestinal species several nosocomial pathobionts due additive effects. Polypharmacy was also associated with microbial functions, including reduction short-chain fatty acid metabolism increased bacterial stress responses. Even nonantibiotic correlated an antimicrobial resistance potential through polypharmacy. Notably, 2-time points dataset revealed alteration recovery response cessation, corroborating observed drug-microbe associations cross-sectional cohort.ConclusionOur large-scale metagenomics unravels extensive disruptive impacts individual exposures microbiome, providing catalog basis for deeper understanding role efficacy toxicity.