Convergent and Divergent Age Patterning of Gut Microbiota Diversity in Humans and Nonhuman Primates.

The gut microbiome has significant effects on healthy aging and aging-related diseases, whether in humans or nonhuman primates. However, little is known about the divergence and convergence of gut microbial diversity between humans and nonhuman primates during aging, which limits their applicability for studying the gut microbiome's role in human health and aging. Here, we performed 16S rRNA gene sequencing analysis for captive rhesus macaques (Macaca mulatta) and compared this data set with other freely available gut microbial data sets containing four human populations (Chinese, Japanese, Italian, and British) and two nonhuman primates (wild lemurs [Lemur catta] and wild chimpanzees [Pan troglodytes]). Based on the consistent V4 region of the 16S rRNA gene, beta diversity analysis suggested significantly separated gut microbial communities associated with host backgrounds of seven host groups, but within each group, significant gut microbial divergences were observed, and indicator bacterial genera were identified as associated with aging. We further discovered six common anti-inflammatory gut bacteria (, , , , and ) that had butyrate-producing potentials suggested by pangenomic analysis and that showed similar dynamic changes in at least two selected host groups during aging, independent of distinct host backgrounds. Finally, we found striking age-related changes in 66 plasma metabolites in macaques. Two highly changed metabolites, hydroxyproline and leucine, enriched in adult macaques were significantly and positively correlated with and . Furthermore, genus-level pangenome analysis suggested that those six common indicator bacteria can synthesize leucine and arginine as hydroxyproline and proline precursors in both humans and macaques. This study provides the first comprehensive investigation of age patterning of gut microbiota of four human populations and three nonhuman primates and found that , , , , , and may be common antiaging microbial markers in both humans and nonhuman primates due to their potential metabolic capabilities for host health benefits. Our results also provide key support for using macaques as animal models in studies of the gut microbiome's role during human aging.