Emerging Role of Gut Microbiota in Modulating Response to Therapies in IBD

The gut microbiota is increasingly recognized as a key contributor in the pathogenesis and progression of inflammatory bowel disease (IBD). Compared with healthy individuals, patients with IBD show marked dysbiosis, characterized by reduced microbial diversity, an expansion of facultative anaerobes such as Proteobacteria, and a depletion of obligate anaerobes within the Firmicutes phylum. These changes have been implicated in the perpetuation of intestinal inflammation, disruption of mucosal immune homeostasis, and altered metabolic functions, further underscoring the microbiota's relevance in IBD pathophysiology. However, microbiota-driven insights have not yet been consistently translated into therapeutic stratification or clinical decision-making. A major challenge lies in the complex and dynamic interplay between the gut microbiota and various treatment modalities, including conventional immunosuppressants, biologics, and small-molecule inhibitors. While accumulating evidence suggests that IBD treatments may modulate microbial composition and function, it remains unclear whether these changes represent a direct pharmacological effect or are secondary to inflammation control. Additionally, there is a lack of comparative data on microbiota profiles associated with differential responses to various therapeutic classes, limiting the implementation of microbiota-informed precision medicine. In this review, we synthesize current evidence on the association between gut microbiota composition and treatment outcomes, focusing on biologic agents and small-molecule therapies. Furthermore, we discuss the potential of microbiota-targeted strategies, such as fecal microbiota transplantation (FMT) and precision probiotics, in enhancing therapeutic response. A deeper understanding of host-microbe interactions could enable a more personalized and effective approach to IBD management.