Genotype Is a Stronger Determinant than Sex of the Mouse Gut Microbiota

Abstract

The mammalian gut microbiota is considered to be determined mostly by diet, while the effect of genotype is still controversial. Here, we examined the effect of genotype on the gut microbiota in normal populations, exhibiting only natural polymorphisms, and evaluated this effect in comparison to the effect of sex. DNA fingerprinting approaches were used to profile the gut microbiota of eight different recombinant inbred mouse lines of the collaborative cross consortium, whose level of genetic diversity mimics that of a natural human population. Analyses based on automated ribosomal internal transcribed spacer analysis demonstrated significant higher similarity of the gut microbiota composition within mouse lines than between them or within same-gender groups. Thus, genetic background significantly impacts the microbiota composition and is a stronger determinant than gender. These findings imply that genetic polymorphisms help shape the intestinal microbiota of mammals and consequently could affect host susceptibility to diseases.

Host genetic and environmental effects on mouse intestinal microbiota

“…Moreover, expression of a human caspase conferred differential susceptibility to Listeria monocytogenes infection in male and female transgenic mice, apparently due to estrogen interactions (Yeretssian et al, 2009). However, Kovacs et al (2011) found no gender differences in the CC mice of their study. As is the case with maternal lineage, undetected genetic or epigenetic factors that were not adequately controlled could manifest in sexbased differences between strains.…”

“…However, siblings of other strains were markedly dissimilar in microbial flora. Recently, DNA fingerprinting techniques revealed no maternal-derived differences in gut bacteria of CC mice (Kovacs et al, 2011). However, Ley et al (2005) found lineage influences to extend to more than one generation.…”

“…Such studies have used both conventionally reared and germ-free animals inoculated selectively with different bacterial isolates or natural microbiota samples. Strong evidence exists that the global host genotype influences specific microbiota composition (beta diversity) (Benson et al, 2010;Kovacs et al, 2011), and mutations and inactivation of specific genes have been associated with discrete community changes, in some cases linked to metabolic diseases (for example, obesity, diabetes and metabolic syndrome) (reviewed in Spor et al (2011)). At the same time, however, studies using embryo transplantation, litter cross-fostering and other variation in mouse rearing and housing have shown that experimental manipulations, environmental and stochastic factors (for example, founder effects) can exert dominating contributions in microbiota taxonomic composition (Friswell et al, 2010).…”

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.…”

Dietary input of microbes and host genetic variation shape among-population differences in stickleback gut microbiota

“…Here, we show that within-and among-population differences in gut microbiota reflect host genetic diversity, even after accounting for differential colonization. We use these findings to infer that metacommunity structure of the stickleback microbiota is more strongly driven by host genotype (likely reflecting species filtering processes (Ley et al, 2008;Benson et al, 2010;Kovacs et al, 2011)) than by colonization.…”