The effect of host genetics on the gut microbiome

Abstract

The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 × 10. Additionally, in a targeted analysis of regions involved in complex diseases, innate and adaptive immunity, or food preferences, 32 loci were identified at the suggestive level of P < 5 × 10. Most of our reported associations are new, including genome-wide significance for the C-type lectin molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 × 10) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. Our results demonstrate the importance of understanding host-microbe interactions to gain better insight into human health.

Patterns of seasonality and group membership characterize the gut microbiota in a longitudinal study of wild Verreaux's sifakas (Propithecus verreauxi)

“…Finally, microbial assemblages may in part be hereditary, as host genotype may influence susceptibility to colonization by certain microbes (Bonder et al., 2016; Kovacs et al., 2011; van Opstal & Bordenstein, 2015; Turpin et al., 2016). However, it remains unclear to which extent host relatedness contributes to microbiota similarity in wildlife, especially in relation to the factors discussed above.…”

Host genetics and microbiome associations from the lens of genome wide association studies

“…Recent studies employing these technologies have uncovered evidence for both environmental and host genetic association with the microbiome composition [8,11,20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. However, to date there is no consensus regarding how and to what extent does host genetics shapes the gut microbiome, as compared to environmental factors.…”

“…This lack of consistency could originate either from differences in the underlying analysis methods or from lack of reproducibility, necessitating further investigation of the reported associations. The only genetic variants consistently shown to be microbiome-associated in multiple mGWAS are located in close proximity to the LCT gene, which is associated with lactase persistence [8,27,30,31,46]. However, while important, this association may be confounded by lactose consumption [46].…”

“…However, a potential shortcoming of the above studies is that they require previous knowledge of associated genes, and thus cannot discover new associations. Thus, recent studies have performed unbiased microbiome-genome wide association studies (mGWAS) spanning 93-1,812 individuals [8,[27][28][29][30][31].…”

Emerging role of intestinal microbiota and microbial metabolites in metabolic control

“…Whether these early life events are determinants of microbiota-related disease in later life remains to be established. Prospective large cohort studies addressing these factors in relation to microbiota composition will provide important insight into the role of the intestinal microbiota in the (patho)physiology of disease [10,11].…”