Lactiplantibacillus plantarum AS21 restores glucose tolerance in aging male mice by increasing gut-derived citrulline production, an effect that correlates with reshaping of mucosal microbial communities. This finding suggests sex-specific metabolic interventions through targeted probiotic strains may address age-related glucose dysregulation differently in men and women.
Key Points
- Aged males show greater glucose intolerance and citrulline depletion than females
- AS21 restores male citrulline levels by expanding microbial citrulline-synthesis genes
- Citrulline supplementation alone improves glucose tolerance and GLP-1 secretion
Longevity Analysis
Age-related glucose dysregulation differs between sexes, and interventions addressing the underlying microbial depletion of a single metabolite show measurable reversal of metabolic decline. Rather than treating glucose intolerance as a unified condition, this work indicates that restoring specific microbial metabolic functions—in this case, amino acid synthesis—can reset downstream hormone signaling and carbohydrate metabolism. This distinction matters for both prevention and intervention in aging populations, particularly where sex differences alter the timing and severity of metabolic aging. The pathway from microbial function to circulating metabolite to systemic glucose control demonstrates how disturbances in one layer of microbial ecology propagate upward into endocrine and metabolic dysfunction.
Original published by Wiley Aging Cell, by Mengya Jia, Mengyan Chen, Hu Chen, Huiling Zhang, Ruixue Dou, Chaorui Wang, Muhammad Ishaq, Xiaoying Wei, Zitong Ding, Xusheng Guo .