Enrichment of Lactic Acid-Producing Bacteria in the Fecal Microbiota of Patients with Ulcerative Colitis in North India

Abstract

Previous studies have established the relationship between the gut microbiota and ulcerative colitis (UC); however, there is a scarcity of data on the fecal microbiome profile of patients with UC in the Indian population. This study aimed to examine the fecal microbiome profile of north Indian patients with UC ( $n=105$ ), including with active disease ( $n=64$ ) and in remission ( $n=41$ ), compared to healthy controls ( $n=36$ ), using 16S rRNA gene sequencing. Both relative abundance analysis and linear discriminant analysis effect size (LEfSe) revealed a significant enrichment of lactic acid-producing facultative anaerobic pathobionts, namely, Bifidobacterium, Lactobacillus, and Streptococcus, in patients with UC (both with active disease and those in remission). Additionally, a significant decrease was observed in anaerobic genera responsible for the synthesis of short-chain fatty acids (SCFAs), especially butyrate, such as Blautia, Roseburia, Lachnospiraceae, and Ruminococcaceae. Differential metabolic pathway analysis using PICRUSt2 confirmed a loss of SCFAs production and increased lactose and nitrate metabolism in UC patients. Biochemical analysis of fecal samples confirmed the increased colonization of nitrate-reducing microbes in UC patients, suggesting inflammation-driven dysbiosis. LEfSe and PICRUSt2 analyses revealed an enrichment of Prevotella and Blautia microbes and the upregulation of two specific metabolic pathways, sulfolactate degradation and reductive acetyl coenzyme A pathway-I, which can distinguish UC patients in remission from those with active disease. Our findings caution against the use of lactic acid-producing bacteria (LABs) and recommend the exploration of butyrate-producing microbes as probiotics to restore SCFAs levels in UC patients.