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The interplay between gut microbiota and drugs primarily occurs via the composition of commensal microbiota, modulation of metabolism processes and the function of intestinal mucosal barrier. Probiotics are promising homeostasis therapies for the gut microbiota during antibiotics-induced imbalance and for drug-metabolizing enzymes. Some bacterially derived metabolic processes of short-chain fatty acids (SCFAs), bile acids (BAs), indole derivatives and polyamines have potential to modulate hosts’ drug metabolism systems. On the other hand, drugs also affect the nutrient status of gut microbiota metabolism. In addition to the metabolites of gut microbiota, the gastrointestinal mucosa barrier also has a certain impact on drug absorption and bioavailability. The major site of interaction in the process of drug absorption is IECs and intestinal barriers. Notably, gut microbiota indirectly affect several functional aspects of the mucosal barriers, including the apical junctional complex (AJC), mucus layer and microfold cells (M cells).

Gut microbiota plays an important role in the gut and have become a hotspot of recent research interests. Commensal microbiota in gut exert a variety of effects on the host, from shaping the structure and function of the gut and the immune system to the modulation of nutrient status of the host and the treatment outcomes of some drugs. Gut microbiota and its enzyme product and subsequent products, such as short-chain fatty acid and bile acid, play important roles in the biotransformation of drugs via directly or indirectly affecting drug absorption, toxicity, metabolism and bioavailability. Drugs, especially antibiotics, also affect the homeostasis of probiotics and the integrity and function of the intestinal mucosa. These interplaying processes produce a variety of important metabolites of the host and drugs and affect the balance of microbiota and the mucosal barrier then modulate the function of drugs. Gut microbiota imbalance is associated with a broad range of disease mechanisms, and this association denotes a new drug-therapeutic avenue. The present review summarizes how gut microbiota acts as an “invisible organ” to directly or indirectly modulate the function of drugs, on the aspects of probiotic homeostasis, drugs and host nutritional metabolism, AJC, mucus layer and microfold cells.