Gut Microbiota Depletion Using Antibiotics to Investigate Diet‐Derived Microbial Metabolites: An Efficient Strategy

Scope Gut microbiota depletion using antibiotics in drinking water is a valuable tool to investigate the role of gut microbes and microbial metabolites in health and disease. However, there are challenges associated with this model. Animals avoid drinking water because of the antibiotic bitterness, which affects their metabolic health. The present study develops an efficient strategy to deplete gut microbes without affecting metabolic parameters. Methods and results Male C57BL/6J mice (7 weeks old) are fed a control (C) or high‐fat (HF) diet. Subgroups of C and HF mice receive an antibiotic cocktail in drinking water (CA and HA). The antibiotic dosage is gradually increased so that the animals adapt to the taste of antibiotics. Metabolic parameters, gut microbiome, and microbial metabolites are assessed after 12 weeks treatment. Culture methods and 16s rRNA amplification confirm the depletion of gut microbes in antibiotic groups (CA and HA). Further, antibiotic treatment does not alter metabolic parameters (body weight, body fat, lean body mass, blood glucose, and glucose/insulin tolerance), whereas it suppresses the production of diet‐derived microbial metabolites (trimethylamine and trimethylamine‐ N ‐oxide). Conclusion This strategy effectively depletes gut microbes and suppresses the production of microbial metabolites in mice without affecting their metabolic health.