Abstract Background The gut microbiota is increasingly recognised as an important determinant of therapeutic response in inflammatory bowel diseases (IBD). Differences in baseline microbial diversity and taxonomic composition may help predict which patients will respond to biologic therapy. This study aimed to evaluate whether baseline gut microbiome profiles are associated with clinical, endoscopic, and histological outcomes in ulcerative colitis (UC) patients treated with vedolizumab. Methods Biologic-naïve patients with moderate to severe UC initiating vedolizumab (n = 20) were enrolled. The median disease duration was 6 years. Stool samples, dietary questionnaires, clinical assessments, laboratory tests, faecal calprotectin, and colonoscopies with biopsies from five colonic segments were collected at baseline (week 0) and week 24. Gut microbiota from stool samples were analysed using metatranscriptomic RNA sequencing, full-length 16S rRNA sequencing, and CRISPR–Cas system–targeted sequencing. Microbial diversity and community structure were evaluated using NMDS ordination, alpha-diversity metrics, and differential abundance testing (DESeq2, ANCOM-BC). Remission was defined using patient-reported outcomes, endoscopic Mayo score, and Nancy histological index. Results Fifteen patients achieved clinical, endoscopic, and histological remission at week 24, while five had persistent active disease. Responders had higher baseline (week 0) alpha diversity and enrichment of anaerobic, short-chain fatty acid (SCFA)–producing taxa, including the genus Dysosmobacter. In contrast, non-responders showed baseline enrichment of opportunistic and pro-inflammatory taxa associated with dysbiosis, including the families Enterobacteriaceae, Morganellaceae, Yersiniaceae, and Peptoniphilaceae, and the genera Peptoniphilus, Finegoldia, Proteus, Trabulsiella, and Escherichia. At week 24, non-responders exhibited persistent histological inflammation (grade 3-4 of Nancy index) and increased mucosal eosinophilia. Conclusion Baseline gut microbiome diversity and composition were associated with treatment outcomes in UC patients receiving vedolizumab. Responders were enriched with SCFA-producing taxa, whereas non-responders exhibited a dysbiotic, inflammation-associated microbial profile. Integrating microbiome profiling with dietary assessment may improve prediction of therapeutic response and support personalised treatment strategies in UC. Conflict of interest: Ms. Malinauskiene, Vaidota: No conflict of interest Aitmanaite, Lina: No conflict of interest Stulpinas, Rokas: No conflict of interest Russo, Giancarlo: No conflict of interest Stundiene, Ieva: No conflict of interest
Malinauskiene et al. (Thu,) studied this question.