Gut microbiota–driven immunometabolic reprogramming in inflammatory bowel disease: a comprehensive review of impaired inflammation resolution and relapse susceptibility
Year: 2026
Type: article
Abstract: Inflammatory bowel disease (IBD) is clinically characterized by alternating periods of relapse and remission. Even after clinical or endoscopic remission has been achieved, dysbiosis, metabolic abnormalities, impaired barrier function, and residual immune activation may persist, indicating that control of inflammation does not necessarily equate to complete restoration of mucosal homeostasis. Recent studies have shown that IBD-associated dysbiosis not only alters microbial composition but also reshapes mucosal nutritional, redox, and metabolic niches through short-chain fatty acids (SCFAs), tryptophan derivatives, bile acids, and other host–microbial co-metabolic signals, thereby inducing immunometabolic reprogramming in macrophages, T cells, B cells, group 3 innate lymphoid cells (ILC3s), and intestinal epithelial cells. Persistent metabolic abnormalities may restrict the transition of immune cells from inflammatory effector states toward clearance, tolerance, and tissue-repair states, while also disrupting efferocytosis, regulatory T-cell (Treg) stability, immunoglobulin A (IgA)- and ILC3-associated mucosal defense, and epithelial mitochondrial function and regeneration. These alterations may consequently impair inflammation resolution and result in incomplete mucosal repair. Even after overt inflammation has subsided, residual abnormalities in the microbiota, immunometabolism, and epithelial barrier may maintain a fragile mucosal homeostatic state that is highly susceptible to perturbation, lowering the threshold for inflammatory reactivation and increasing susceptibility to relapse. This review focuses on the bidirectional crosstalk between the gut microbiota and immunometabolism, systematically summarizing its roles in impaired inflammation resolution, insufficient restoration of mucosal homeostasis, and IBD relapse. We further discuss potential therapeutic strategies, including microbiota reconstruction, restoration of microbial metabolic functions, immunometabolic modulation, and epithelial repair, with the aim of providing a mechanistic framework and new therapeutic perspectives for sustained remission and relapse prevention in IBD.
Source: Frontiers in Microbiology
Authors: Ruyi Zhang, Lili Zhang, Biwei Chen, Shaozong Chen
Institution: Shandong University of Traditional Chinese Medicine
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225744205