Host genomic variation shapes gut microbiome diversity in threespine stickleback fish

Abstract

Variation among host-associated microbiomes is well documented across species, populations, and individuals. Understanding relationships between host-genetic and microbial variation is important for predicting coevolutionary dynamics between hosts and their microbiota and is also biomedically relevant to understanding why some humans are more susceptible to chronic disorders like Inflammatory Bowel Diseases (IBD). Unfortunately, the relative contributions of host genetics and the environment to microbiome variation have been difficult to study. Human research shows that genetic variation influences microbiome differences but confounding environmental effects cannot be controlled experimentally. Isogenic laboratory models can be used in controlled environments but often focus on large-effect mutations and do not recapitulate genetic variation observed in nature. Thus, although important factors impacting the microbiome have been identified, few studies have tested for the direct influence of natural host-genetic variation on microbiome differences within a controlled environment. To address this, we performed a common garden experiment using laboratory lines of genetically divergent populations of threespine stickleback fish - an outbred model organism commonly used for determining the genetic basis of complex traits in the context of natural genetic variation. Using germ-free derivation of divergent lines and hybrids between them in this experimental framework, we detected a clear, positive association between stickleback genetic dissimilarity and microbiome dissimilarity. With RAD-seq data we identified regions of the genome that contributed most significantly to this relationship. Importantly, we also highlight that heritable morphological traits like body size -when correlated with microbiome composition - need consideration in future host-associated microbiome studies.

A zebrafish model to elucidate the impact of host genes on the microbiota

“…A substantial number of studies have documented general effects, often as associations, of host genetic background on the microbiota in various experimental and ecological contexts including at the species level (Sylvain et al., 2022), inter‐individual level (Boutin et al., 2014), or population level (Kurilshikov et al., 2021; Lopera‐Maya et al., 2022; Small et al., 2023; Smith et al., 2015). Here, host‐associated microbiota is defined as all the microbes and their abundances that can preside within and on the host at any given point in time (Lund et al., 2022; Velasquez et al., 2023).…”