The Philosopher’s Stool: Gut Microbes from Young Mice Counteract Age-Linked Cognitive Deficits

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The Philosopher’s Stool: Gut Microbes from Young Mice Counteract Age-Linked Cognitive Deficits

The swirling universe of microbes in our gut is an essential regulator of immunity and brain health. But age dramatically alters the bustling, diverse gut microbiome, causing poorer health and frailty in elderly populations. Yet, we know little about how the trillions of microbes in our gut affect brain health and immunity during aging processes and if the microscopic inhabitants of this gastrointestinal metropolis can be manipulated to improve health and longevity.

Research from APC Microbiome Ireland at University College Cork introduces a novel approach to reverse aspects of aging-related deterioration in the brain and cognitive function via these gut microbes. The study shows that transplants of fecal matter housing gut microbes from young mice reversed aging-linked changes in the brain’s immunity and cognitive behavior. Yes, you read that right: the fountain of youth, elixir of life, philosopher’s stone, or whatever name for a potion bestowing eternal youth may be found in poop...well, sort of. These results, published in the prominent international journal Nature Aging, reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.

Senior author Professor John F. Cryan says, “Previous research published by the APC and other groups internationally has shown that the gut microbiome plays a key role in aging and the aging process. This new research is a potential game-changer, as we have established that the microbiome can be harnessed to reverse age-related brain deterioration. We also see evidence of improved learning ability and cognitive function”.

Young fecal matter transplants offset behavioral changes linked to aging

Young fecal matter transplants offset behavioral changes linked to aging

This study, led by co-first authors Dr. Marcus Boehme and Ph.D. students Katherine E. Guzzetta and Thomaz Bastiaansen, examined whether transplantation of fecal matter, a vessel for gut microbes, from young mice can ameliorate aging-induced impairments to brain health and function. To do so, Boehme and colleagues collected fecal matter from naive young mice (3–4 months) and transplanted this into aged mice (19–20 months.) A separate group of aged mice received fecal matter from naive old mice to control for the effects of handling during transplantation. To allow aging-associated comparisons, naive young mice received the same young fecal microbiota transplantation mixture.

As a baseline, the APC Microbiome Ireland researchers established that there were differences in microbiota and immunity linked to the age of the mice. When they transplanted fecal matter from young mice to old ones, they saw a reversion of features related to the microbiome and immunity. For example, the composition and diversity of the microbiome in old mice as well as the immune cell profiles in the brain and periphery rejuvenated with fecal matter transplantation from young mice. 

What’s more, the fecal microbiota transplantation from young to old mice had a plethora of effects on the hippocampus, the brain region associated with learning and memory, including the generation of brain cells (neurogenesis) and behavior. To dissect the effects of fecal matter transplants on hippocampus-related behavior, Boehme and colleagues assessed short-term working memory and short-term recognition memory.

They found that fecal microbiota transplantation from young donors rescued aging-associated deficits regarding recognizing novel objects and their ability to solve mazes. Furthermore, in a social interaction test, aged mice receiving old fecal microbiota transplants spent significantly less time in the chamber with a social partner than their young counterparts that received young fecal microbiota transplants.

Additionally, while Boehme and colleagues did not observe an age effect on anxiety-like behavior, young fecal microbiota transplantation dramatically still improved behavior linked to anxiety. This could indicate a potential anxiety-alleviating therapeutic effect of young fecal microbiota transplantation in an aged host. Overall, these data suggest that young fecal microbiota transplantation can rescue specific aspects of aging-induced impairments in behavior.

They found that fecal microbiota transplantation from young donors rescued aging-associated deficits regarding recognizing novel objects and their ability to solve mazes.

The microbiome may be a suitable therapeutic target to promote healthy aging

APC Director Prof Paul Ross stated that “This research of Prof. Cryan and colleagues further demonstrates the importance of the gut microbiome in many aspects of health, and particularly across the brain-gut axis where brain functioning can be positively influenced. The study opens up possibilities in the future to modulate gut microbiota as a therapeutic target to influence brain health.”

“It’s almost like … we could press the rewind button on the aging process,” says John Cryan, a neuroscientist at University College Cork who led the new study. Although very exciting, Cryan cautions that “it is still early days, and much more work is needed to see how these findings could be translated in humans.”

Ideally, to translate these findings to humans, scientists will sift through the myriad of gut microbes, whittling the list down to a handful of culprits that can be administered to humans through sanitary supplements and not a stranger’s smelly stool sample.

Show references

Boehme, M., Guzzetta, K.E., Bastiaanssen, T.F.S. et al. Microbiota from young mice counteracts selective age-associated behavioral deficits. Nat Aging 1, 666–676 (2021). https://doi.org/10.1038/s43587-021-00093-9

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