Abstract Background The global incidence of ulcerative colitis (UC) continues to rise, driven by the complex interplay between genetic susceptibility and environmental factors. The gut microbiota, as a key environmental factor, plays a central role in regulating intestinal mucosal immune responses. However, clinical strategies that effectively integrate microbiome research with personalized dietary interventions remain insufficient. Methods Integrated metagenomic and dietary platform analyses were employed to identify key differences in the expression of microbial dietary degradation genes involved in diet-microbiota co-metabolism. Functional validation was performed using molecular assays and murine models. Additionally, single-cell metabolic analysis was utilized to investigate cellular responses to dietary changes and microbial interactions, providing deeper insights into the metabolic pathways activated by dietary fiber degradation. Results UC patients exhibited significant reductions in Bacteroides uniformis and xyloglucan-degrading enzymes. Supplementation with B. uniformis and xyloglucan promoted the production of cysteine, enhancing Treg cell function and restoring immune homeostasis. Single-cell analysis further revealed that B. uniformis and dietary antigens regulate the composition of the T cell receptor (TCR) repertoire and influence T cell differentiation, thereby impacting immune response regulation and disease progression. Conclusion This study proposes an innovative “Microbiome–Enzyme–Diet–Immunometabolism” strategy for precision nutritional intervention, offering new insights into UC pathogenesis and identifying novel avenues for targeted nutritional therapy. References: 1.Hoffmann Sardá F A, Giuntini E B, Oliveira A, et al. Baseline intestinal microbiota composition influences response to a real-world dietary fiber interventionJ. npj Biofilms and Microbiomes, 2025, 11(1): 203. 2.Arnoldini M, Sharma R, Moresi C, et al. Quantifying the varying harvest of fermentation products from the human gut microbiotaJ. Cell, 2025, 188(19): 5332-5342. e16. 3.Wu M, McNulty N P, Rodionov D A, et al. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut BacteroidesJ. Science, 2015, 350(6256): aac5992. 4.Yi J, Jung J, Horton D, et al. A hierarchy of intestinal antigens instructs the CD4+ T cell receptor repertoireJ. Immunity, 2025, 58(5): 1217-1235. e4. Conflict of interest: Dr. Jiang, Lingjuan: No conflict of interest Cao, Yubin: No conflict of interest Bai, Xiaoyin: No conflict of interest Ruan, Gechong: No conflict of interest Yang, Hong: No conflict of interest
Jiang et al. (2026) studied this question.