Dataset Information

Does MHC heterozygosity influence microbiota form and function?

ABSTRACT: MHC molecules are essential for the adaptive immune response, and they are the most polymorphic genetic loci in vertebrates. Extreme genetic variation at these loci is paradoxical given their central importance to host health. Classic models of MHC gene evolution center on antagonistic host-pathogen interactions to promote gene diversification and allelic diversity in host populations. However, all multicellular organisms are persistently colonized by their microbiota that perform essential metabolic functions for their host and protect from infection. Here, we provide data to support the hypothesis that MHC heterozygote advantage (a main force of selection thought to drive MHC gene evolution), may operate by enhancing fitness advantages conferred by the host's microbiome. We utilized fecal 16S rRNA gene sequences and their predicted metagenome datasets collected from multiple MHC congenic homozygote and heterozygote mouse strains to describe the influence of MHC heterozygosity on microbiome form and function. We find that in contrast to homozygosity at MHC loci, MHC heterozygosity promotes functional diversification of the microbiome, enhances microbial network connectivity, and results in enrichment for a variety of microbial functions that are positively associated with host fitness. We demonstrate that taxonomic and functional diversity of the microbiome is positively correlated in MHC heterozygote but not homozygote animals, suggesting that heterozygote microbiomes are more functionally adaptive under similar environmental conditions than homozygote microbiomes. Our data complement previous observations on the role of MHC polymorphism in sculpting microbiota composition, but also provide functional insights into how MHC heterozygosity may enhance host health by modulating microbiome form and function. We also provide evidence to support that MHC heterozygosity limits functional redundancy among commensal microbes and may enhance the metabolic versatility of their microbiome. Results from our analyses yield multiple testable predictions regarding the role of MHC heterozygosity on the microbiome that will help guide future research in the area of MHC-microbiome interactions.

SUBMITTER: Khan MAW

PROVIDER: S-EPMC6522005 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Does MHC heterozygosity influence microbiota form and function?

Khan M A Wadud MAW Stephens W Zac WZ Mohammed Ahmed Dawood AD Round June Louise JL Kubinak Jason Lee JL

PloS one 20190516 5

MHC molecules are essential for the adaptive immune response, and they are the most polymorphic genetic loci in vertebrates. Extreme genetic variation at these loci is paradoxical given their central importance to host health. Classic models of MHC gene evolution center on antagonistic host-pathogen interactions to promote gene diversification and allelic diversity in host populations. However, all multicellular organisms are persistently colonized by their microbiota that perform essential meta ...[more]

PMID: 31095603

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Project description:In monogamous species that exhibit extensive biparental investment, such as termites, both sexes are predicted to be selective when choosing a mate. Size-related traits are expected to be important in partner selection because the fat reserves of the colony founders sustain the incipient colony. Partner relatedness and heterozygosity determine the degree of inbreeding and genetic diversity within the colony and may thus also influence partner selection. To test these predictions, we investigated whether phenotypic and genetic traits influence mate choice and/or competitive advantage during pair formation of Formosan subterranean termites, Coptotermes formosanus (Isoptera: Rhinotermitidae). Pair formation in termites normally occurs within a short period after swarming when alates form tandem pairs on the ground. Alates were collected from 5 light trap samples in the French Quarter of New Orleans, LA. From each sample, both tandem pairs and single individuals were collected and their sex, body weights, and head widths were recorded. Pairwise relatedness and individual levels of heterozygosity were determined by microsatellite genotyping. Males in tandem pairs with females had a significantly larger head width than males that did not form tandem pairs. Weights as well as head widths of tandem running partners were positively correlated. For the majority of the samples, relatedness between tandem partners did not differ from the relatedness to members of the other tandem pairs. Thus, no kin discrimination occurred during tandem running. However, females engaged in tandem running had a higher degree of heterozygosity than females that remained single. These findings suggest partner selection and/or competitive advantage based on size-related phenotypic parameters and genetic diversity. The pairing advantage of heterozygous females might explain previous findings of sex-biased alate production depending on the degree of inbreeding in colonies of several species of the genus Coptotermes.

Project description:AIMS:The gut microbiota is believed to play important roles in the health of pregnant mammals, including their nutrient metabolism, immune programming and metabolic regulation. However, until recently, the shifts in gut microbiota composition and faecal and blood metabolic activity during different stages of pregnancy had not been investigated. METHODS AND RESULTS:We investigated the shifts in backfat thickness, plasma and faecal metabolites and gut microbiota on days 30, 60, 90 and 110 of pregnancy and on day 21 after parturition (weaning) in sows. The backfat thickness of sows did not significantly differ among the different stages of pregnancy. The plasma concentrations of lipid metabolites, including triacylglycerol (TG), total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and calcium were reduced (P < 0·05) during pregnancy. In addition, the concentration of these metabolites, except TG, reached their maximum at the time of weaning. We also found that Tenericutes, Fibrobacteres and Cyanobacteria varied significantly according to the stages of pregnancy in sows (P < 0·05). Most of the genera, such as Clostridiales, Desulfovibrio, Mogibacteriaceae and Prevotella, increased (P < 0·05) with the progression of pregnancy and decreased (P < 0·05) at weaning. The alpha diversity values (i.e., Shannon diversity and observed species) of sow gut microbiota increased (P < 0·05) from pregnancy to weaning. Pregnancy stages also significantly influenced (P < 0·05) the community structure (beta diversity) of gut microbiota. The progression of pregnancy was associated with changes in lipid metabolism and several carbohydrate-degradation bacteria (i.e., Prevotella, Succinivibrio, Bacteroides and Parabacteroides). CONCLUSIONS:Although causal links between the measured parameters remain hypothetical, these findings suggest that the increased diversity and concentration of beneficial gut microbes are associated with the metabolism of pregnant sows. SIGNIFICANCE AND IMPACT OF THE STUDY:Manipulation of the sow gut microbiota composition may potentially influence metabolism and health during pregnancy.

Dataset Information

Does MHC heterozygosity influence microbiota form and function?

Publications

Does MHC heterozygosity influence microbiota form and function?

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