Gut dysbiosis influences the pathophysiology of multiple sclerosis: A case-control study from North India.

Background And Objectives: Alterations in gut microbiota have been linked to pathophysiology of immune-mediated diseases like multiple sclerosis (MS). This study was undertaken to characterise the gut microbiome profile in North Indian MS patients and to evaluate gut health using biomarkers like zonulin (intestinal permeability) and calprotectin (intestinal inflammation).

Methods: 84 Patients with relapsing-remitting MS patients (RRMS) of 18-75 years of age with an expanded disability status scale (EDSS) score less than or equal to 5.5 and 106 healthy controls (HC) were recruited for the study. Gut microbiota was sequenced using Illumina MiSeq. Clinical, demographic, anthropometric, and dietary details were recorded. Sandwich ELISA was used to quantify serum zonulin and fecal calprotectin levels.

Results: MS patients had lower alpha microbial diversity, while distinct beta diversity metrics were observed in MS and HC. Firmicutes was found to be the most abundant phylum in both groups with significant enrichment in MS than HC. In MS, significant depletion of commensal bacterial species like Faecalibacterium prausnitzii, Monoglobus pectinilyticus, and Bacillus species indicated gut dysbiosis. These alterations influenced the prevalence and functioning of metabolic pathways. Therefore, pathways involved in biosynthesis of long-chain fatty acids (LCFA) were significantly enriched in MS than HC, while generation of short-chain fatty acids were predominant in HC. In addition, high zonulin, without an increase in calprotectin levels was observed in MS patients.

Conclusions: RRMS patients in North India have a decreased microbial diversity in terms of depletion of commensals. The dominance of LCFA generating pathways in MS patients might have triggered the proinflammatory reactions, that are possibly linked to the development of a highly permeable/leaky gut in MS.