Cynomolgus Macaques and Humans Exhibit Broadly Similar Age-Related Changes in the Gut Microbiome

The relative sizes of gut microbial populations are known to change significantly with age; harmful bacteria become more numerous while beneficial bacteria become less numerous. This results in greater chronic inflammation and a lowered production of beneficial metabolites. Numerous causes are proposed for this shift in the microbiome, from dietary changes characteristic of aging to declining immune function, but it is far from clear as to the relative contribution of each such mechanism. In the years ahead we might expect to see strategies emerge to reverse age-related changes in the microbiome, such as application of fecal microbiota transplantation to providing old people with young microbial populations, or the delivery of beneficial bacterial populations in pill form.

Previous clinical and rodent studies have suggested that age may affect the composition of the gut microbiota. Here, monkeys were used to investigate this issue and this animal model has the following advantages: (i) the microbial composition of monkeys is highly similar to that of humans, which makes it easier to translate these findings into human research; (ii) it can effectively avoid the influences of confounding factors such as living environment and genetic background; (iii) nonhuman primates exhibit similar key life span metrics as humans. Here, we characterized the composition and function of the gut microbiota at three representative age phases, which is a new development in this field.

Our results showed that the diversity of the gut microbiota in cynomolgus macaques was reduced with age, which was consistent with previous human studies. Moreover, we found that the microbial composition of the three groups was significantly different. Firmicutes and Bacteroidetes were the dominant phyla in both humans and cynomolgus macaques. Similar to human studies, we found that, compared with the young and adult groups, the old group showed a slight increase in Firmicutes, whereas Bacteroidetes gradually decreased after youth.

With increased age, the relative abundances of Veillonellaceae and Coriobacteriaceae were significantly increased, and Ruminococcaceae and Rikenellaceae were significantly decreased at the family level. There is evidence to confirm that the family Veillonellaceae is associated with age-related diseases such as atherosclerosis and stroke. Ruminococcaceae play a vital role in the maintenance of gut health through degrading cellulose and hemicellulose components of plant material by CAZymes and transporters. These compounds are fermented and converted into short-chain fatty acids (mainly acetate, butyrate, and propionate), which are absorbed by the host and are important for metabolic and immunological homeostasis. Our finding showed that the relative abundance of Ruminococcaceae was negatively correlated with age. Consistent with our findings, previous studies showed that Ruminococcaceae, one of the core microbiota, becomes less abundant in older people, whereas some taxa associated with unhealthy aging emerge. These findings suggested that Ruminococcaceae may have a positive effect on the aging process.



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