Fecal Microbiota Transplant from Young Mice Improves Cognitive Function in Old Mice

The gut microbiome shifts with age, reducing beneficial populations and increasing harmful populations that contribute to chronic inflammation. Today's research materials can be added to other examples in which an intervention to restore a more youthful gut microbiome in old animals results in improved function, both through a reduction in inflammation and increased production of beneficial metabolites such as butyrate, that promotes increased levels of BDNF and neurogenesis, among other effects. It is a challenge to pick apart which of the mechanisms are most influential, but restoring a more youthful gut microbiome is clearly beneficial.

Fecal microbiota transplantation from young to old is an approach to the treatment of aspects of aging that could be comparatively rapidly rolled out in human medicine, in principle at least, given that such transplants are already used for cases in which the gut is overtaken by pathological bacteria. It isn't the only potential treatment with evidence to support its benefits. Innoculation with flagellin provokes the immune system into better gardening the gut microbiome, removing more of the pathological species, and also has some safety data in human patients already as a result of use as a vaccine adjuvant. More speculatively, it should be possible to achieve similar results via high dose probiotics, though here there is a lot more work to do with regard to establishing the right mix, dose, approach to delivery. It is entirely plausible that none of the products presently available in the marketplace can be combined to achieve the desired result.

Fecal transplants reverse signs of brain aging in mice

To test whether a young microbiome could reverse signs of aging, researchers took fecal samples from 3- to 4-month-old mice, the equivalent of young adults, and transplanted them into 20-month-old animals - ancient by mouse standards. The scientists fed a slurry of feces to the old mice using a feeding tube twice a week for 8 weeks. As controls, old mice received transplants from fellow old mice, and young from young. The first thing the team noticed was that the gut microbiomes of the old mice given young mouse microbes began to resemble those of the younger ones. The common gut microbe Enterococcus became much more abundant in old mice, just as it is in young mice, for example.

There were changes in the brain as well. The hippocampus of old mice - a region of the brain associated with learning and memory - became more physically and chemically similar to the hippocampus of young mice. The old mice that received young mouse poop also learned to solve mazes faster and were better at remembering the maze layout on subsequent attempt. None of these effects was seen in old mice given old mouse feces.

Microbiota from young mice counteracts selective age-associated behavioral deficits

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.


A bit off-topic, but related to slowing cognitive aging and neurodegeneration with the regeneration drug, MSI-1436, is this new USPTO patent application ---



Posted by: L Pagnucco at August 19th, 2021 2:08 AM

So how often does one have to take in the poop slurry to gain the benefits? In the future, will we be buying designer slurries from top athletes, scientists etc. . .

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level

I wonder if high IQ people, entrepreneurs, extraordinarily happy people, young people of centenarian lineage have distinct microbiomes / fecal matter compositions. I also wonder whether some corresponding benefits of distinct microbiomes might transfer via FMT.

Posted by: Brad at August 20th, 2021 6:32 PM
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