Gut Microbiota as a Potential Modulator of Response to Biologic and Small-Molecule Therapies in Inflammatory Bowel Disease

The therapeutic landscape of inflammatory bowel disease (IBD) has expanded substantially with the development of biologic and small-molecule therapies. Nevertheless, many patients fail to respond to these treatments or experience a secondary loss of response. The mechanisms underlying treatment failure remain incompletely understood. Given the ability of gut microorganisms to modify therapeutic compounds, sustain pro-inflammatory immune activation, alter intestinal barrier function and produce bioactive metabolites, the gut microbiota may represent an important modulator of therapeutic response. To summarize current evidence on the role of the gut microbiota in response to biologic and small-molecule therapies in IBD, with particular emphasis on potential mechanisms of drug–microbiota interactions and their implications for treatment response and non-response. Accumulating evidence suggests that the gut microbiota may influence therapeutic efficacy through direct modification of drugs and indirect effects mediated by host immunity, intestinal barrier function and microbial metabolites. Microbial signatures associated with response to individual biologic therapies have been identified, although findings remain heterogeneous. Emerging evidence also indicates that non-bacterial components of the gut ecosystem may contribute to treatment response. The gut microbiota represents a biologically plausible modulator of therapeutic response in IBD. Integration of microbiome data with host genetic and immunological features may help identify biomarkers capable of predicting response to individual therapeutic agents.