Predominant Role of Host Genetics in Controlling the Composition of Gut Microbiota

Abstract

BackgroundThe human gastrointestinal tract is inhabited by a very diverse symbiotic microbiota, the composition of which depends on host genetics and the environment. Several studies suggested that the host genetics may influence the composition of gut microbiota but no genes involved in host control were proposed. We investigated the effects of the wild type and mutated alleles of the gene, which encodes the protein called pyrin, one of the regulators of innate immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), which is characterized by recurrent self-resolving attacks of fever and polyserositis, with no clinical signs of disease in remission.Methodology/Principal FindingsA total of 19 FMF patients and eight healthy individuals were genotyped for mutations in the MEFV gene and gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis. These analyses demonstrated significant changes in bacterial community structure in FMF characterized by depletion of total numbers of bacteria, loss of diversity, and major shifts in bacterial populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla in attack. In remission with no clinical signs of disease, bacterial diversity values were comparable with control but still, the bacterial composition was substantially deviant from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct grouping, which depended on the allele carrier status of the host.Conclusions/SignificanceThis is the first report that clearly establishes the link between the host genotype and the corresponding shifts in the gut microbiota (the latter confirmed by two independent techniques). It suggests that the host genetics is a key factor in host-microbe interaction determining a specific profile of commensal microbiota in the human gut.

Host genetic and environmental effects on mouse intestinal microbiota

“…Some of these studies address fine genetic scales, such as monozygotic, human twins (Turnbaugh et al, 2009) and wellcharacterized host mutations (Vaahtovuo et al, 2005;Khachatryan et al, 2008). Others have addressed the effects of host genetics on the gut microbiome on a larger scale with studies of species of primates (Ley et al, 2008a;Ochman et al, 2010) and various animals in captivity or the wild (Ley et al, 2008a).…”

Bacterial communities of disease vectors sampled across time, space, and species

“…These measures have suggested that community assemblages correlate with salinity , diet (Ley et al, 2008), pH (Jones et al, 2009;Lauber et al, 2009), and host genotype (Khachatryan et al, 2008). We used a similar approach to explore the factors affecting bacterial community assembly in prairie dog fleas sampled across space and time.…”

Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors

“…These diseases are well understood to be multifactorial, with both environmental and genetic components (11)(12)(13), and the contribution of the gut microbiota is currently viewed as an environmental factor (14). Although a number of studies have suggested that composition of the gut microbiota may be subject to host genetic forces, existing evidence is conflicting and confounded by the genetic diversity of vertebrate (especially human) populations and strong environmental effects (15)(16)(17)(18)(19).…”