Are MEFV gene variants linked to differences in gut bacteria?

Details

The human gastrointestinal tract hosts a highly diverse symbiotic microbiota whose composition depends on host genetics and the environment. Earlier studies had suggested an influence of host genetics on gut microbiota composition, but had not proposed genes involved in host control. The researchers investigated how wild-type and mutated alleles of MEFV, the gene encoding pyrin, a regulator of innate immunity, related to the composition of gut commensal bacteria.

MEFV mutations cause familial Mediterranean fever (FMF, MIM249100), an autoinflammatory disorder marked by recurring, self-resolving attacks of fever and polyserositis; there are no clinical signs of disease during remission. The researchers genotyped 19 FMF patients and eight healthy individuals for MEFV mutations and assessed gut bacterial diversity using 16S rRNA gene library sequencing and FISH analysis.

During attacks, FMF was associated with significant changes in bacterial community structure, including depletion of total bacterial numbers, loss of diversity and major shifts in populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla. During remission, when there were no clinical signs of disease, bacterial diversity values were comparable to those of controls, but bacterial composition still differed substantially from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct groups depending on the host's allele carrier status.

The authors described this as the first report clearly establishing a link between host genotype and corresponding shifts in gut microbiota, with the shifts confirmed by two independent techniques. They suggested that host genetics is a key factor in host–microbe interaction that determines a specific profile of commensal microbiota in the human gut.