# Host immunogenetic variation and gut microbiome functionality in a wild vertebrate population

## TL;DR

This study explores how genes in the immune system of wild birds influence the types and functions of gut microbes, revealing trade-offs in microbial defense and metabolism.

## Contribution

The study is the first to investigate how MHC genes shape gut microbiome functionality in a wild vertebrate population.

## Key findings

- MHC-II diversity and a specific MHC-I allele affect gut microbiome taxonomy, altering the abundance of specific bacterial species.
- Higher MHC-I diversity is linked to increased microbial defense genes and reduced metabolism genes in the gut microbiome.
- Functional gut microbiome networks are more fragmented in individuals with higher MHC-I diversity.

## Abstract

The gut microbiome (GM) –important for host health and survival– is partially shaped by host immunogenetics. However, to date, no study has investigated the influence of host Major Histocompatibility Complex (MHC) genes on gut microbiome functionality in a wild population. Here we use a natural population of the Seychelles warbler (Acrocephalus sechellensis) to assess the effects of MHC genes on GM taxonomy and functionality using shotgun metagenomics.

Our results show that taxonomic GM composition was associated with MHC-II diversity and the presence of one specific MHC-I allele (Ase-ua 7). Specifically, MHC-II diversity was associated with decreased Lactococcus lactis and increased Staphylococcus lloydii abundance, while Ase-ua 7 was linked to reduced Enterococcus casselifavus and Gordonia sp OPL2 but increased Escherichia coli and Vulcaniibacterium thermophilum. These taxonomic changes may reflect differences in MHC-mediated microbial recognition. In contrast, functional GM composition was significantly associated with increasing individual MHC-I diversity but not MHC-II diversity. In particular, increasing MHC-I diversity was associated with an increased prevalence of microbial defence genes but a reduced prevalence of microbial metabolism genes. Analysis also revealed that functional GM networks were more fragmented in high compared to low MHC-I diversity hosts.

These results suggest that MHC variation (particularly at MHC-I) plays an important role in shaping both the taxonomy and function of the GM in wild vertebrates. In the Seychelles warbler, this results in trade-offs whereby there is an increase in microbial defence and a reduction in GM metabolic potential in individuals with higher MHC-I diversity. Thus, this work sheds light on the possible costs and benefits of maintaining a healthy microbiome, which is essential for understanding how the GM and immune system co-evolve.

Video Abstract

Video Abstract

The online version contains supplementary material available at 10.1186/s40168-026-02341-9.