Identification of mucosal microbiome-host gene interactions in ulcerative colitis patients

Abstract

Abstract The role of gut microbiota in clinical applications, such as markers for diagnosis, prognosis prediction, and therapeutic agents in inflammatory bowel disease, is still unclear. Here, we analyzed the mucosal microbiome, which can discriminate between the active state of moderate-to-severe ulcerative colitis (UC) and normal state, and explored the correlations between microbes and host genes by integrating 16s RNA sequencing and RNA sequencing in the colonic mucosa of UC patients and healthy controls. Correlation analyses were performed between the mucosal microbiome and host gene expression, followed by a network analysis. The DEG results showed that 28 and 18 genes were expressed at higher levels in the UC and normal groups, respectively. GSEA revealed 1,857 gene sets to be enriched in the UC group. In UC, we found a higher abundance of taxa such as genera Lactobacillus and Neisseria and less abundance of species such as Bacteroides coprocola, Bacteroides phlebeius, and Parabacteroides merdae. Significant positive gene-taxa correlations were observed between Lactobacillus and REG4 (Spearman rho = 0.86), Bacteroides coprocola and NBR1 (Spearman rho = 0.75), Bacteroides plebeius and COLCA2 (Spearman rho = 0.77), and Parabacteroides merdae and UTX-AS1 (Spearman rho = 0.74). Our results provide the basis for the role of microbiota in colonic mucosa in the initial development of UC, and the integrated analysis of the host microbiome and genes can serve as a biomarker for diagnosis and treatment target in UC patients.