Neoagarotetraose Supplementation Improves Gut Microbiome to Extend Life in Mice

With advancing age, the balance of microbial populations in the intestinal tract changes to favor harmful, pro-inflammatory species at the expense of those that produce beneficial metabolites. This contributes to the onset and progression of age-related conditions. Here find an interesting example of adjustment of the aging gut microbiome in mice, promoting beneficial microbial populations to result in extended life span. We'd expect mouse life span to be more plastic to this class of intervention than human life span, but nonetheless, work on preventing detrimental age-related changes to the gut microbiome is demonstrating its worth in animal models. Researchers should now focus on obtaining more human data on the effects of fecal microbiota transplant from young to old individuals, as this is the most clearly effective approach to date, with the greatest amount of existing human safety data.

Dietary oligosaccharides can impact the gut microbiota and confer tremendous health benefits. The aim of this study was to determine the impact of a novel functional oligosaccharide, neoagarotetraose (NAT), on aging in mice. 8-month-old C57BL/6J mice as the natural aging mice model were orally administered with NAT for 12 months. The preventive effect of NAT in Alzheimer's disease (AD) mice was further evaluated. Aging related indicators, neuropathology, gut microbiota and short-chain fatty acids (SCFAs) in cecal contents were analyzed.

NAT treatment extended the lifespan of these mice by up to 33.3%. Furthermore, these mice showed the improved aging characteristics and decreased injuries in cerebral neurons. Dietary NAT significantly delayed DNA damage in the brain, and inhibited reduction of tight junction protein in the colon. A significant increase at gut bacterial genus level (such as Lactobacillus, Butyricimonas, and Akkermansia) accompanied by increasing concentrations of SCFAs in cecal contents was observed after NAT treatment. Functional profiling of gut microbiota composition indicated that NAT treatment regulated the glucolipid and bile acid-related metabolic pathways. Interestingly, NAT treatment ameliorated cognitive impairment, attenuated amyloid-β (Aβ) and Tau pathology, and regulated the gut microbiota composition and SCFAs receptor-related pathway of Alzheimer's disease (AD) mice.

In conclusion, NAT mitigated age-associated cerebral injury in mice through gut-brain axis. The findings provide novel evidence for the effect of NAT on anti-aging, and highlight the potential application of NAT as an effective intervention against age-related diseases.


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