Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis

• Published in: Gut microbes Vol. 16; no. 1; p. 2336877
• Main Authors: Zhu, Jinlin, Yin, Jialin, Chen, Jing, Hu, Mingyi, Lu, Wenwei, Wang, Hongchao, Zhang, Hao, Chen, Wei
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2024; Taylor & Francis Group
• Subjects: Animals; biomarker selection; Colitis; Colitis, Ulcerative; Gastrointestinal Microbiome; Genome-scale metabolic model; Humans; inflammatory bowel disease; Inflammatory Bowel Diseases; Machine Learning; Mice; N-acetyl-D-mannosamine; Parabacteroides merdae ATCC 43184; Research Paper; ulcerative colitis; N-acetyl-D-mannosamine; Parabacteroides merdae ATCC 43184; ulcerative colitis; Genome-scale metabolic model; machine learning; inflammatory bowel disease; biomarker selection
• ISSN: 1949-0976; 1949-0984; 1949-0984
• DOI: 10.1080/19490976.2024.2336877

Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.