Transplanting Gut Microbes from Long-Lived Humans into Mice to Assess the Outcomes

It is well known that the gut microbiome is influential on long-term health, and undergoes detrimental changes with advancing age. Beneficial species decline, while inflammatory and otherwise unhelpful species prosper. The reasons for these changes are not well understood, but probably involve a combination of many factors, such as diet, immune dysfunction, and so forth. There is a growing interest in the research community in assessing the contribution of gut microbiome changes to degenerative aging, and finding ways to reverse those changes.

The study noted here is less interesting for the presented data, and more interesting for demonstrating that one can in fact transplant gut microbes from a human to a mouse and expect to see results that mimic the quality of the human microbiome. Thus transplants from long-lived humans - with what is assessed via other measures to be a better, more youthful, more diverse gut microbiome - leads to healthier mice than is the case for transplants from an average older person with a more degraded gut microbiome. That this can be accomplished might lead to faster progress towards treatments that adjust the gut microbiome to a more beneficial state.

The most direct, blunt approach to therapy is some form of fecal microbiota transplant from young donor to old individual. In short-lived animal species, this resets the gut microbiome to a more youthful state and extends healthy life. In human medicine, fecal microbiota transplants are already carried out for severe conditions in which the gut is overtaken by pathological microbes. The challenges in implementation largely involve screening out undesirable microbes that a young donor can keep suppressed but an old recipient would struggle with. A possibly better approach would be a probiotic strategy of some sort, in which large volumes of desirable microbes are provided orally, encapsulated in a way that allows for their survival into the gut. These classes of therapy are close to practical realization, at present only lacking the will and the funding to move ahead.

Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria

The interactions between gut microbiota and their host have become a popular topic in research. There is growing evidence to suggest that a close relationship exists between gut microbiota and aging. Age-related changes in gut microbiota occur widely among animals, with evidence of this ranging from insects to mammals. Human-based studies have revealed a trend in age-related microbiota features, which shows an increase in gut microbiota diversity from infants to adults, followed by a decrease as adults age. Researchers found signatures of extreme longevity in gut microbiota composition that were related to extreme aging. Others found 11 features shared among long-living Chinese and Italian people, including higher alpha diversity and operational taxonomic units (OTUs); they also showed that long-living people had greater gut microbiota diversity than a younger group among Chinese and Japanese populations.

High microbiota diversity has been associated with good health in general. Early research on the gut microbiota of elderly people has indicated that healthier subjects have significantly greater gut microbiota diversity than those in long-term residential care. Overall, the information obtained from studies such as these suggests that long-living people can serve as an acceptable model to investigate whether gut microbiota is a feasible target for promoting healthy aging. However, the exact roles that the microbiota play still require investigation.

Studies in animal subjects have shown that age-related microbiota can affect the lifespan of the host. Ten-day-old and 30-day-old Drosophila were used as microbiota donors for 10-day-old Drosophila. The lifespan of the 10-day-old transplant group lived significantly longer than the 30-day-old transplant group, and had a decreased frequency in intestinal barrier dysfunction. Subsequently, researchers transplanted the gut contents of young and old African turquoise killifish to old fish. Consistent with the results from Drosophila, fish transplanted with feces from young donors had a longer lifespan and were significantly more active. These results suggest that the gut microbiota of young individuals can slow host aging and prolong the lifespan of the tested species.

In the current study, the hypothesis that the gut microbiota of long-living people has the ability to delay host aging compared with those of average lifespan, is tested. To test this hypothesis, the gut microbiota of long-living (L group) and typical aging elderly people were transplanted into antibiotic-treated mice, which were then analyzed for differences in gut microbiota and aging indices. L group mice demonstrated greater microbiota diversity and beneficial bacteria, such as probiotic genera and short-chain fatty acid producers. Importantly, aging-related indices, such as lipofuscin and β-galactosidase accumulation, were less in the L group. Our experiment provided primary evidence that the gut microbiota of long-living people has the ability to delay host aging.