Breakthrough discoveries link gut microbiota and age-related decline

Though only thus far proven in mice, a recently published study revealed some astonishing results about the connection between gut microbiota and the performance of an aging brain.

Specifically, a recently published study in the journal Nature Aging found that older mice transplanted with the gut microbiota of younger mice displayed improved cognitive function and behavior. The older mice performed better in a key test of their mental and physical abilities, and notably also developed gut bacteria similar to their younger donors.

While the procedure of transferring microbiota has been shown in fish to improve lifespan and motor behavior (eLife. 2017;6:e27014), the mice researchers noted it is not known whether microbiota from young donors can restore aging-associated impairments in mammals.

How exactly do you transplant microbiota from one organism to the other, you might ask.

For the mice researchers, the process involved fecal microbiota transplantation, or FMT—where fecal pellets from three- or four-month-old mice (similar in the lifecycle to a healthy 18-year-old human) are collected, snap-frozen on dry ice, and eventually implanted into 19- or 20-month-old mice (parallel to a healthy 70-year-old human).

Following the transplants, older mice who received the borrowed microbiota outperformed their counterparts in the Morris Water Maze, a test of spatial learning and memory where mice are submerged in water and have to find their way to a platform.

Aging triggers metabolic and immune changes that lead to unrest in the brain when it comes to function and behavior (Neurosci Biobehav Rev. 2017;79:66-86), the study authors noted. But the transplant of microbiota from their young donor mice seemed to reverse aging-associated differences in peripheral and brain immunity in the implanted mice, the study found. The data suggested that FMT could restore age-associated changes in the activation of microglia, which essentially are the immune cells of the central nervous system (CNS).

Researchers also looked at metabolites associated with the hippocampus in the mice receiving transplants, and found that 35 metabolites that had been altered by aging were restored toward pre-aged levels by FMT.

Because the hippocampus in mammals is key to spatial learning and memory—areas where the effects of aging are often readily seen—study authors projected their data could potentially translate into benefits around cognition, though they admitted more targeted research is still needed.

 “Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging,” they surmised.

While the study of FMT in mice provided some fascinating results, it follows on some limited research that has probed whether human gut microbiota may provide a potential avenue to enhance cognition. A 2020 narrative review of that human research found that the “available evidence suggests that gut microbiota is linked to cognitive performance and that manipulation of gut microbiota could be a promising avenue for enhancing cognition. (Nutrients. 2020;12[10]:3009).”