Could Horizontal Gene Transfer of CoB12 in Gut Flora Affect Pathogenesis in MS?

The prevalence of coenzyme B12 (CoB12) biosynthetic genes in gut bacteria and phages may play a role in disease pathogenesis in multiple sclerosis (MS), according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, held in San Diego, California, from February 23 to 25.

Some evidence has suggested that dysbiosis of bacterial communities in the gut contributes to MS pathology, however, the exact kind of community imbalances that may be responsible for disease pathology have not been elucidated.

For the study, researchers from the University of Tokyo in Japan performed metagenomic and metabolomic analyses of stool samples sourced from a Japanese cohort of patients (n=60) with MS and healthy control individuals (n=30).

Compared with control individuals, patients with MS were found to have a significant reduction in CoB12 biosynthetic genes in bacteria and phages.

In the gut, CoB12 is a cofactor of the catalytic enzyme involved in the biosynthetic propionate pathway and propionate is thought to induce intestinal anti-inflammatory regulatory T cells in the intestines.

In these data, compared with control individuals, patients with MS were found to have a significant reduction in propionate concentration in a metabolomic analysis.

Among those with MS, the abundance of CoB12 biosynthetic genes positively correlated with fecal propionate concentrations and negatively correlated with disease progression parameters.

In the genomic analysis, integration of the CoB12 biosynthetic genes into the bacterial host chromosome was observed, suggesting horizontal gene transfer of CoB12 in MS.

“We show that a reduction of the bacterial CoB12 biosynthetic genes might be linked to a reduction of propionate concentration in the gut of MS patients. Interestingly, CoB12 biosynthetic genes are encoded in temperate phages, suggesting that these genes are spreading to the gut microbiome by horizontal gene transfer,” the researchers noted.

They added, “Our findings provide novel insights into the symbiotic relationship among humans, bacteria, and phages related to the MS pathogenesis.”

The findings of this study may not be generalizable for a more diverse population. These findings should be confirmed among an independent cohort.