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Updated: Jan 25, 2026

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice
Published on: September 19, 2019
Microbiota from young mice restore the function of aged ISCs
Kodandaramireddy Nalapareddy1, David B Haslam2, Ann-Kathrin Kissmann3
1Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA.
Abstract:
Homeostasis in the intestinal epithelium depends on intestinal stem cells (ISCs). A reduction in the function of ISCs, caused by a decline of canonical Wnt signaling in ISCs, contributes to a reduced regenerative potential of the aged intestine. The composition of the intestinal microbiota changes upon aging. We report here that aging-associated changes in the composition of the microbiota result in reduced canonical Wnt signaling through Ascl2 in ISCs, which causes a decline in the regenerative potential of aged ISCs in vivo. We demonstrate, using microbiota transfer experiments, that interestingly, elevated levels of Akkermansia muciniphila in the intestine cause a reduction of Ascl2-mediated canonical Wnt signaling in ISCs and thus reduced regeneration of the aged epithelium. The composition of the intestinal microbiota thus plays a critical role in regulating the function of ISCs. Our data imply potential therapeutic approaches via modulation of the composition of microbiota for aging-associated changes in the function of ISCs.
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