Age, Sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model.
Abstract
We evaluated the impact of sex and mitochondrial-haplotype on the age-related changes in the fecal gut microbiome of the genetically heterogeneous rodent model, the OKC-HETB/W rat. Alpha-diversity, measuring richness and evenness of gut microbiome composition, did not change with age or mitochondrial-haplotype. However, beta-diversity, a measure of microbial differences among samples, was significantly modulated by age in male and female rats in both mitochondrial-haplotypes. The age-related changes in the microbiome differed markedly between male and female rats. Five microbial species changed significantly with age in male rats compared to nine microbial species in female rats. Only three of these microbes changed with age in both male and female rats. The mitochondrial-haplotype of the rats also affected how aging altered the microbiome. Interestingly, most of the microbial species that changed significantly with age were mitochondrial-haplotype and sex specific, i.e., changing in one sex and not the other. We also discovered that sex and mitochondrial-haplotype significantly affected the age-related variations in content of fecal short-chain fatty acids and plasma metabolites that influence or are regulated by the microbiome, e.g., tryptophan derived metabolites and bile acids. This study demonstrates that the hosts sex plays a significant role in how the gut microbiome evolves with age, even within a genetically diverse background. Importantly, this is the first study to show that the mitochondrial-haplotype of a host impacts the age-related changes in the microbiome and supports previous studies suggesting a bidirectional interaction between the gut microbiome and host mitochondria.
HighlightsMost age-related changes in microbial species occurred in one sex but not the other
Mitochondrial-haplotype altered the microbiome and was generally sex dependent
Microbiome associated metabolites differed by age, sex, and mitochondria-haplotype
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Research summary
The paper investigates the influence of sex and mitochondrial-haplotype on age-related changes in the gut microbiome, which is relevant to understanding the biological mechanisms of aging. While it provides solid research on the interaction between host factors and microbiome composition, the findings are somewhat incremental and do not directly address root causes of aging or lifespan extension. The study contributes to the field by highlighting the complexity of microbiome dynamics with age, but its overall impact is limited.
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