Microbiota from young mice restore the function of aged ISCs.

Kodandaramireddy Nalapareddy, David B Haslam, Ann-Kathrin Kissmann, Theresa Alenghat, Selina Stahl, Frank Rosenau, Yi Zheng, Hartmut Geiger

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA. Electronic address: [email protected]. · pubmed

Paper

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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Research summary

The paper claims that changes in the intestinal microbiota composition can influence the regenerative potential of aged intestinal stem cells through modulation of canonical Wnt signaling. This research is relevant as it addresses the underlying mechanisms of aging and suggests potential therapeutic strategies to enhance regenerative capacity in aged tissues.

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