Microbiome Transplants Between Young and Old

Aging and intestinal dysfunction are correlated in lots of organisms spanning from insects, to mammals, to humans. This is characterized by increased permeability in the intestinal barrier and a decrease in microbial diversity. This loss of microbiome diversity has several causes including diet and dysfunction in the immune system[1].

The amount of intestinal dysfunction with age varies between individuals. Based on this, researchers have explored whether there are differences in the intestinal microbiota of long-lived people. There is some evidence for this. In one study, researchers analyzed the microbiomes of long-lived Chinese and Italians. They had greater microbiota diversity and more operational taxonomic units (a measure of the number of species)[2].

This inspires the question of whether the microbiome from a person exhibiting good health and longevity could be beneficial on its own. We do know that the microbiomes of young organisms are beneficial compared to old microbiomes. For example, a fecal transplant on a 10-day old fly into another 10-day old fly results in a longer lifespan and less intestinal permeability than a transplant from a 30-day old fly into a 10-day old fly[3]. And it's not just flies. You see similar results in other organisms like killifish[4].

So, what about transplants from those who are aging well? To find out, researchers took fecal samples from long-lived humans and transplanted them into mice. This resulted in an increase in microbiota diversity. Moreover, there was also an increase in species considered to be beneficial like short fatty acid chain producers. They saw a reduction in some age indices, markers we see with aging, including a decrease in lipofuscin and beta-galactosidase[5].

Based on these results, it would be beneficial to characterize the species existing in long-lived people. Fecal transplants are rarely used and are not the goal of this research. Beyond the general ick factor, there is a lot of risk of introducing pathogens through it. However, research like this could spearhead the design of new probiotics that might promote healthier aging. Once we know what makes a microbiome pro-longevity, this might be possible.

Sources

1. Transplanting Gut Microbes from Long-Lived Humans into Mice to Assess the Outcomes. Fight Aging! https://www.fightaging.org/archives/2020/04/transplanting-gut-microbes-from-long-lived-humans-into-mice-to-assess-the-outcomes/ (2020).

2. Kong, F. et al. Gut microbiota signatures of longevity. Curr. Biol. 26, R832–R833 (2016).

3. Clark, R. I. et al. Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality. Cell Rep. 12, 1656–1667 (2015).

4. Smith, P. et al. Regulation of life span by the gut microbiota in the short-lived African turquoise killifish. eLife 6, (2017).

5. Chen, Y. et al. Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria. Aging 12, 4778–4793 (2020).