Supplementing the guts of older mice with poop from younger ones has revealed the key role microbes play in intestinal stem cell function.

After receiving a fecal microbiota transplant from younger mice, one aspect of age-related decline in the guts of older mice was reversed, driven by increased intestinal stem cell activity that maintains the intestinal walls.

The findings suggest that such transplants could someday be a treatment pathway for age-related intestinal conditions, such as inflammation and obesity.

"As we age, the constant replacement of intestinal tissue slows down, making us more susceptible to gut-related conditions," says molecular biologist Hartmut Geiger of Ulm University in Germany. "Our findings show that younger microbiota can prompt older intestine to heal faster and function more like younger intestine."

Intestinal stem cells are crucial for maintaining a stable, healthy gut. They’re the mechanism by which the gut lining – the epithelium – constantly replenishes and renews itself, ensuring consistent gut function.

However, as we age, the rate of this renewal slows, increasing vulnerability to age-related gut dysfunction.

In previous research, Geiger and his colleagues, cell biologists Yi Zheng and Kodandaramireddy Nalapareddy of Cincinnati Children’s Hospital Medical Center, determined that this slowed regeneration is directly linked to reduced function of intestinal stem cells.

We also know that the microbial communities that live in our guts change with age, with such changes linked to conditions like Parkinson’s disease, Alzheimer’s disease, and even vision loss. The researchers wanted to know if the gut microbiome affects stem cell activity, too.

So, they recruited more team members and designed a simple experiment to test it: transplanting fecal samples between and within groups of old mice and young mice.

After the series of transplants was complete, the researchers studied the intestines to see what changes, if any, resulted from the transfer.

In the older mice, the change was dramatic. Stem cell activity had increased, as well as the Wnt signalling that these cells need in order to function. The regeneration of the epithelium picked up pace – and, critically, the gut healed more quickly after radiation damage.

"This reduced signaling causes a decline in the regenerative potential of aged ISCs," Zheng says. "However, when older microbiota were replaced with younger microbiota, the stem cells resumed producing new intestine tissue as if the cells were younger. This further demonstrates how human health can be affected by the other life forms living inside us."

In the younger mice, the change was less dramatic. There was only a slight drop in stem cell activity, Wnt signalling, and regeneration; the intestines continued to function reasonably well. This suggests that the aging gut is far more sensitive to microbiome changes than younger ones.

Another really interesting finding was that one of the perpetrators of stem cell curtailment in the aging gut is Akkermansia, a bacterium that is generally considered beneficial in several ways, with signs that it can help reduce diet-induced obesity and depression-like behavior in mice.

In aging mice, elevated levels of *Akkermansia *actually contribute to the suppression of Wnt signalling – a finding that implies that gut bacteria are not necessarily good or bad, but that their contribution may depend on context.

This isn’t a slam-dunk for human health; our bodies (and intestines) are more complex than those of mice, and we’d need to perform separate studies to see if this phenomenon occurs in our own species.

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However, the research does illuminate a promising avenue for future study.

It also suggests that age-related stem cell decline may not be irreversible. By harnessing the ability of gut microbes to shape how intestinal tissue renews itself, scientists could one day develop ways to help preserve intestinal health as we age.

The research has been published in Stem Cell Reports.