Lactobacillus paracasei L9 Improves Amino Acid Absorption in Aged Mice via Enhanced LAT2 Expression Through the...

Background: Aging is frequently accompanied by disrupted amino acid homeostasis, contributing to malnutrition and physical function decline in elderly individuals. However, age-related impairment of intestinal absorptive capacity limits the efficacy of protein supplementation alone to improve nutritional status. Gut microflora diversity is regarded as a key factor for nutrient absorption. Lactobacillus paracasei L9 (L9) has recently been shown to improve gut health, but its effects on intestinal amino acid absorption remain unclear. Methods: In this study, 15-month-old male C57BL/6J mice (n = 4 per group) were administered L9 (4 × 10¹⁰ CFU in 100 μL) via daily gavage for 9 months to investigate the effect of L9 on amino acid absorption. Results: After L9 intervention, both plasma amino acid levels and the expression of large neutral amino acid transporter 2 (LAT2), a key transporter associated with neutral amino acid absorption, were significantly increased. Subsequently, microbiota composition analysis revealed that L9 modulated the gut microbiota, increasing the abundance of multiple beneficial bacteria in aged mice. Targeted metabolomics then revealed that plasma concentrations of butyric acid significantly elevated in aged mice after L9 intervention. Furthermore, IEC-6 cells experiments were conducted, demonstrating that butyric acid can enhance LAT2 expression via activating the Akt/mTOR pathway. Conclusions: Overall, these results suggested that L9 significantly enhanced amino acid absorption capacity in aged mice via the butyric acid-Akt/mTOR-LAT2 axis, and this identifies potential targets for improving age-related malnutrition and providing a promising strategy to maintain amino acid homeostasis in the elderly.