Huang Ying-Chen, Lu Hsin-Yi, Zhang Li, Olivier Alicia, Wu Tung-Lung, Hsu Chuan-Yu, LeGrand Caleb, Zeng Huawei, Curran Samantha, Wang Qingzhou, Nannapaneni Ramakrishna, Zhang Xue, Ticó Max, Mariotti Marco, Wu Ryan T Y, Combs Gerald F, Cheng Wen-Hsing
Department of Biochemistry, Nutrition, and Health Promotion, Mississippi State University, Mississippi State, Mississippi, USA.
Department of Poultry Science, Mississippi State University, Mississippi State, Mississippi, USA.
Aging Cell. 2025 Aug;24(8):e70130. doi: 10.1111/acel.70130. Epub 2025 Jun 20.
Previous studies have shown that dietary selenium (Se) deficiency in mice reshapes gut microbiota, exacerbates healthspan deterioration (e.g., type 2 diabetes), and paradoxically activates beneficial longevity pathways. This study demonstrated that dietary Se deficiency accelerated many age-related gut microbial changes in aged telomere-humanized C57BL/6J diabetic mice in a sexually dimorphic manner, with Akkermansia muciniphila showing the greatest enrichment in males. However, dietary Se deficiency did not enrich A. muciniphila in mature or middle-aged male C57BL/6J wild-type mice. Oral gavage of A. muciniphila alleviated Se deficiency-induced type 2 diabetes-like symptoms, reversed mucosal barrier dysfunction and gut inflammation, and resulted in a trend of symbiotic and competitive suppression changes in certain gut bacteria in mature wild-type mice under conventional conditions. The beneficial effects of A. muciniphila appeared to be independent of selenoproteins sensitive to dietary Se deficiency, such as GPX1, SELENOH, and SELENOW, in the liver and muscle. Altogether, these results show that dietary Se deficiency accelerates age-related A. muciniphila enrichment specifically in aged male mice with severe insulin resistance and pancreatic senescence, indicating a potential hormetic response to Se deficiency through reshaped gut microbiota, which alleviates hyperglycemia and partially compensates for healthspan decline.
先前的研究表明，小鼠饮食中硒（Se）缺乏会重塑肠道微生物群，加剧健康寿命的恶化（如2型糖尿病），但矛盾的是会激活有益的长寿途径。本研究表明，饮食中硒缺乏以性别二态性方式加速了老年端粒人源化C57BL/6J糖尿病小鼠许多与年龄相关的肠道微生物变化，其中嗜黏蛋白阿克曼氏菌在雄性小鼠中富集程度最高。然而，饮食中硒缺乏并未使成熟或中年雄性C57BL/6J野生型小鼠体内的嗜黏蛋白阿克曼氏菌富集。对成熟野生型小鼠进行常规条件下的口服灌胃嗜黏蛋白阿克曼氏菌，可缓解硒缺乏诱导的2型糖尿病样症状，逆转黏膜屏障功能障碍和肠道炎症，并导致某些肠道细菌出现共生和竞争性抑制变化趋势。嗜黏蛋白阿克曼氏菌的有益作用似乎独立于肝脏和肌肉中对饮食硒缺乏敏感的硒蛋白，如GPX1、SELENOH和SELENOW。总之，这些结果表明，饮食中硒缺乏会加速与年龄相关的嗜黏蛋白阿克曼氏菌富集，特别是在患有严重胰岛素抵抗和胰腺衰老的老年雄性小鼠中，这表明通过重塑肠道微生物群对硒缺乏存在潜在的 hormetic 反应，可缓解高血糖并部分补偿健康寿命的下降。
