Dietary selenium deficiency accelerates the onset of aging-related gut miccrobial changes in aged Telomere-humanized mice, with {Akkermansia muciniphila} being the most prominent & alleviating selenium deficiency-induced Type

Authors: HUANG, YING-CHEN - Mississippi State University; LU, HSIN-YI - Mississippi State University; ZHANG, LI - Mississippi State University; OLIVIER, ALICIA - Mississippi State University; WU, TUNG-LUNG - Mississippi State University; HSU, CHUAN-YU - Mississippi State University; LEGRAND, CALEB - Mississippi State University; Zeng, Huawei; CURRAN, SAMANTHA - Mississippi State University; WANG, QINGZHOU - Mississippi State University; NANNAPANENI, RAMAKRISHNA - Mississippi State University; ZHANG, XUE - Mississippi State University; TICO, MAX - University Of Barcelona; MARIOTTI, MARCO - University Of Barcelona; WU, RYAN T.Y. - University Of Maryland; COMBS, GERALD F. JR - Tufts University; CHENG, WEN-HSING - Mississippi State University

Submitted to: Aging Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/2025
Publication Date: 6/20/2025
Citation: Huang, Y., Lu, H., Zhang, L., Olivier, A., Wu, T., Hsu, C., Legrand, C., Zeng, H., Curran, S., Wang, Q., Nannapaneni, R., Zhang, X., Tico, M., Mariotti, M., Wu, R., Combs, G., Cheng, W. 2025. Dietary selenium deficiency accelerates the onset of aging-related gut miccrobial changes in aged Telomere-humanized mice, with {Akkermansia muciniphila} being the most prominent & alleviating selenium deficiency-induced type 2 diabetes. Aging Cell. Article. 0:e70130. https://doi.org/10.1111/acel.70130.
DOI: https://doi.org/10.1111/acel.70130

Interpretive Summary: Selenium (Se) is an essential nutrient for humans and animals. Optimal Se intake is necessary for overall health, but the nutritional requirement varies by confounding factors such as age, disease, and sex. There are more than 33 million Americans have type 2 diabetes, which is a disease where human body cannot use energy from food properly. Recent studies suggest that both insufficient and excessive Se intakes may potentially raise the risk of type 2 diabetes. In the present study, our results demonstrate that Se deficiency reshapes gut microbiota and induces health deterioration, and gut bacteria (A. muciniphila) can alleviate hyperglycemia and health deterioration. The information will be useful for scientists and health-care professionals who are interested in nutrition and type-2 diabetes prevention.

Technical Abstract: Dietary selenium (Se) deficiency in mice reshapes gut microbiota and induces healthspan deterioration (e.g., type-2 diabetes) but, paradoxically, beneficial pathways towards longevity. Here, we showed that dietary Se deficiency accelerated many age-dependent gut microbial changes in old telomere-humanized mice in a sexually dimorphic manner, with Akkermansia muciniphila exhibiting the greatest enrichment in the males. Although dietary Se deficiency did not enrich A. muciniphila in mature or middle-aged male mice, oral gavage of this bacterium resulted in symbiotic and antibiotic changes, alleviated type 2 diabetes like symptoms, and reversed mucosal barrier dysfunction and gut inflammation in the mice fed a Se-deficient diet under an antibiotic-pretreated or a conventional condition. The beneficial roles of A. muciniphila appeared to be independent of such selenoproteins sensitive to dietary Se deficiency as GPX1, SELENOH, and SELENOW in the liver and muscle. Furthermore, A. muciniphila feeding alleviated hyperglycemia in streptozotocin-induced diabetes in male pigs. Collectively, our results demonstrate enrichment of A. muciniphila by dietary Se deficiency specific in old male mice displaying insulin resistance and pancreatic failure, suggesting a hormetic response to dietary Se deficiency through reshaped gut microbiota to alleviate glycemia and compensate for healthspan deterioration.