Youth may be wasted on the young, but not elderliness—not when the elderliness manifests in the gut as a mature microbiome. In experiments led by scientists in Singapore, gut microbes from old mice (24 months old) were transplanted into young, germ-free mice (6 weeks old). After eight weeks, the young mice had increased intestinal growth and production of neurons in the brain, known as neurogenesis.
The research team, which was based at Nanyang Technological University (NTU), showed that the increased neurogenesis was due to an enrichment of gut microbes that produce a specific short chain fatty acid, called butyrate. The scientists suggest that butyrate helps the old mice counter some of aging’s debilitating effects. In addition, the scientists speculate that butyrate-enriched foods could help slow aging, benefiting the young—and possibly the old and butyrate-deprived, too.
Details of the new research appeared November 13 in the journal Science Translational Medicine, in an article titled, “Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice.”
“The higher concentration of gut microbiota–derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21),” the article’s authors wrote. “An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling.”
Butyrate, which is produced through microbial fermentation of dietary fibers in the lower intestinal tract, stimulates production of FGF21, a prolongevity hormone that plays an important role in regulating the body’s energy and metabolism. As we age, butyrate production is reduced.
“Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice,” the authors continued. “These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.”
In other words, giving butyrate on its own to the young germ-free mice had the same adult neurogenesis and intestinal growth effects. Commenting on the neurogenesis effects, Sven Pettersson, an NTU professor, offered the following: “We’ve found that microbes collected from an old mouse have the capacity to support neural growth in a younger mouse. This is a surprising and very interesting observation, especially since we can mimic the neurostimulatory effect by using butyrate alone.
“These results will lead us to explore whether butyrate might support repair and rebuilding in situations like stroke and spinal damage, and to attenuate accelerated aging and cognitive decline.”
The researchers were also intrigued by the intestinal growth effects, which could counter age-related reductions in the viability of small intestinal cells. Such reductions are associated with reduced mucus production that makes intestinal cells more vulnerable to damage and cell death.
According to the researchers, the addition of butyrate could improve intestinal barrier function and reduce the risk of inflammation. The team found that mice receiving microbes from the old donor gained increases in length and width of the intestinal villi—the wall of the small intestine. In addition, both the small intestine and colon were longer in the old mice than the young germ-free mice.
The discovery shows that gut microbes can compensate and support an aging body through positive stimulation. This points to a new potential method for tackling the negative effects of aging by imitating the enrichment and activation of butyrate.
“We can conceive of future human studies where we would test the ability of food products with butyrate to support healthy aging and adult neurogenesis,” noted Pettersson. “In Singapore, with its strong food culture, exploring the use of food to ‘heal’ ourselves, would be an intriguing next step, and the results could be important in Singapore’s quest to support healthy aging for their silver generation.”
The current study builds on Pettersson’s earlier studies on how transplantation of gut microbes from healthy mice can restore muscle growth and function in germ-free mice with muscle atrophy, which is the loss of skeletal muscle mass.