Age-related changes in the gut microbiota impair intestinal stem cell function

A new study led by Hartmut Geiger at the University of Ulm, Germany, and Yi Zheng and Kodandaramireddy Nalapareddy, Cincinnati Children's Hospital Medical Center (CCHMC), USA reveals that age-related changes in the gut microbiota directly impair intestinal stem cell (ISC) function and that restoring a youthful microbial environment can reverse this decline. The results were published today in Stem Cell Reports. 

Cells lining the intestine are constantly renewed to maintain tissue integrity, nutrient absorption, and regenerative capacity following injury. This process is driven by ISCs, which divide and mature to produce the cells of the intestinal lining. With aging, ISC activity declines, which contributes to the emergence of age-related intestinal conditions such as impaired nutrient absorption, regenerative capacity, and increased inflammation – key contributors to age-associated intestinal dysfunction. 

The researchers found that ISCs in old mice were significantly less active than those in young mice, resulting in diminished intestinal cell replenishment and impaired regeneration after injury. In their new study, the showed that changes in the function of ISCs coincided with pronounced differences in the composition of the gut microbiota between young and aged mice.

To test whether these microbial changes directly influenced stem cell function, the team restored a more youthful microbiota in old mice by transferring gut microbiota from young donors. This intervention reversed the age-related decline in ISC activity, leading to improved regenerative responses following intestinal injury. The researchers further identified a bacterial species enriched in the aged microbiota that appeared to inhibit ISC function, providing mechanistic insight into how specific microbial shifts contribute to stem cell aging.

The findings demonstrate that the gut microbiota are a regulator of intestinal stem cell function and that age-related stem cell decline can be reversible.

The study underscores the microbiota as a critical, modifiable determinant of intestinal homeostasis and tissue regeneration. By linking microbial composition to stem cell activity, the research highlights host-microbe interactions as a potential therapeutic target to preserve intestinal function, enhance regenerative capacity, and promote healthy aging.