Abstract Background Gut microbial dysbiosis in ulcerative colitis (UC) exhibits substantial inter-individual heterogeneity, yet the delineation of patterns and their clinical implications remain poorly understood. We hypothesized that understanding distinct dysbiotic pathotypes and their longitudinal variability may help elucidate microbiome–disease interactions and improve patient stratification. Methods Fecal microbiome data from a previously reported longitudinal cohort of UC patients treated with adalimumab (ADA) and healthy controls 1 were analyzed, with dysbiosis defined by the median beta-diversity distance to controls. Microbial communities were clustered into ecotypes based on network analysis to identify distinct dysbiotic pathotypes contributing to dysbiosis. Gut microbial variability was assessed through intra-individual beta-diversity. Subgroup of samples have been processed with shotgun metagenomics for functional profiling. Results Substantial heterogeneity in gut dysbiosis was observed among UC patients, separating them into dysbiotic and less dysbiotic groups. Ecotype-based analysis using baseline samples revealed five distinguishable dysbiotic pathotypes characterized by enrichment of facultative anaerobes, including a cluster dominated by Gammaproteobacteria (e.g., Escherichia and Pantoea spp.) and another by Enterococcaceae (e.g., Enterococcus spp.), as well as clusters enriched with oral-origin bacteria (e.g., Actinomyces spp. and Rothia), environmental taxa (e.g., Ralstonia spp.), and lactate-producing bacteria (e.g., Lactobacillus spp.). Patients who achieved long-term clinical remission at week 56 exhibited a significant decrease in specific dysbiotic pathotypes, whereas the non-remission group did not. Microbiome variability was significantly associated with disease duration, with long-standing UC patients exhibiting lower overall compositional change and enrichment of genes associated with response to stress environment in metagenomic functional profiles. Conclusion This study identifies several distinct dysbiotic pathotypes in UC patients, where specific ecotypes showing characteristic microbial signatures. The change of these pathotypes over time was linked to treatment outcomes. Long-term disease duration shaped less variability of microbiome and functional genes enriched in stress environment. Together, these findings indicate that UC-associated dysbiosis and its association with clinical outcomes are not uniform but vary by pathotypes and longitudinal dynamics. Reference: 1. Oh HN, Shin SY, Kim JH, et al. Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets. Gut Pathog. 2024;16(1):44. Published 2024 Aug 26. doi:10.1186/s13099-024-00637-5 Conflict of interest: Prof. Shin, Seungyong: N/A Jung, Yeonjae: Yeonjae Jung is employees of CJ Bioscience, Inc. Oh, Hyun-Seok: Hyun-Seok Oh is employees of CJ Bioscience, Inc Choi, Chang Hwan: N/A
Shin et al. (Thu,) studied this question.