Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.

Characterization of Changes and Driver Microbes in Gut Microbiota During Healthy Aging Using A Captive Monkey Model.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable confounding effects, and recapitulate age-dependent changes in the gut microbiota of healthy primates. Herein we performed 16S rRNA gene sequencing, characterized the age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed the lifelong dynamic changes of the primate gut microbiota. While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium, the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants, underlining their potential role in host development. Importantly, topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity, and its tremendous decline with age could probably be linked to healthy aging. Moreover, we identified key driver microbes responsible for such age-dependent network changes, which were further linked to altered metabolic functions of lipids, carbohydrates, and amino acids, as well as phenotypes in the microbial community. The current study thus demonstrates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota, and provides new insights into their roles in the development and healthy aging of their hosts.