The gut lining is continually renewed by intestinal stem cells, but as we age these cells become less effective at renewing and repairing the intestine. Now, a study in mice shows that a youthful gut microbiota can improve the regenerative function of aged intestinal stem cells.

The findings, published in Stem Cell Reports, suggest that argeting the gut microbiota could help improve gut repair in aging or disease.

Intestinal stem cells produce new cells that eventually become the various specialized cells of the gut. Aging not only reduces the function of these stem cells, it also alters the intestinal microbiota, which can contribute to digestive problems and other conditions. However, the exact interactions between gut microbes and stem cell aging are not yet fully understood.

To address this question, researchers led by Kodandaramireddy Nalapareddy at the University of Cincinnati in Ohio altered the microbiota of mice using antibiotics and fecal transplants between young and aged animals.

Boosting regeneration

Gut microbes are known to control a key signaling system called Wnt, which helps intestinal stem cells maintain and repair the gut lining. When mice were treated with antibiotics or raised without any gut microbes, Wnt signaling decreased. 

Transferring gut microbes from young mice into older animals boosted Wnt signaling and improved the function of intestinal stem cells. When aged mice received fecal transplants from young mice, their stem cells showed stronger activity, more cell division, and better regeneration after damage.

Instead, transferring gut microbes from old mice into younger animals had only a small effect on signaling and regeneration, the researchers found. 

Rejuvenating cells

In mice, certain microbes that become more common in aged intestines, such as Akkermansia muciniphila, were able to reduce Wnt signaling in intestinal stem cells and impair their regenerative function. This effect also involved changes in other microbial species that interact with A. muciniphila. 

The findings indicate that a youthful microbiota can boost the regenerative function of aged stem cells, but the exact interactions between microbes and intestinal stem cells need more research, the authors say.

“Our data imply potential therapeutic approaches via modulation of the composition of microbiota for aging-associated changes in the function of [intestinal stem cells].”