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Does MHC heterozygosity influence microbiota form and function?

M A Wadud Khan1, W Zac Stephens2, Ahmed Dawood Mohammed3

  • 1Department of Biology, University of Texas at Arlington, Arlington, Texas, United States of America.

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This summary is machine-generated.

MHC heterozygosity enhances microbiome function and connectivity, boosting host fitness. This suggests MHC genes influence health through beneficial interactions with gut microbes, not just pathogen defense.

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Area of Science:

  • Immunogenetics
  • Microbiome Research
  • Evolutionary Biology

Background:

  • Major Histocompatibility Complex (MHC) molecules are crucial for adaptive immunity and exhibit extreme genetic diversity.
  • Traditional models link MHC evolution to host-pathogen interactions, but the role of the host microbiome is increasingly recognized.
  • MHC heterozygote advantage is a key evolutionary force, but its mechanisms remain debated.

Purpose of the Study:

  • To investigate the hypothesis that MHC heterozygote advantage enhances host fitness by modulating the gut microbiome.
  • To explore the impact of MHC heterozygosity on microbiome structure, function, and its association with host health.

Main Methods:

  • Analysis of fecal 16S rRNA gene sequences and predicted metagenomes from MHC congenic homozygote and heterozygote mouse strains.
  • Comparison of microbiome diversity, network connectivity, and functional profiles between MHC genotypes.
  • Correlation analysis between microbiome characteristics and host fitness indicators.

Main Results:

  • MHC heterozygosity promotes functional diversification and enhances microbial network connectivity in the microbiome.
  • MHC heterozygote microbiomes show enrichment for functions positively associated with host fitness.
  • Taxonomic and functional microbiome diversity are positively correlated in MHC heterozygotes, indicating greater functional adaptability.

Conclusions:

  • MHC heterozygosity enhances host health by functionally diversifying the microbiome and increasing its metabolic versatility.
  • MHC heterozygosity may limit microbial functional redundancy, leading to a more robust and adaptive microbiome.
  • These findings highlight a novel mechanism for MHC heterozygote advantage, linking immune gene evolution to microbiome-mediated host fitness.