Lactiplantibacillus plantarum CCFM8610 mitigates oxidative stress-related intestinal aging through its metabolite indole-3-lactic acid

Reducing intestinal oxidative stress presents a promising approach to mitigating intestinal senescence. Lactiplantibacillus plantarum CCFM8610 has been reported to attenuate cadmium-induced intestinal dysfunction and demonstrate significant antioxidant properties. However, its effectiveness and underlying mechanisms in modulating intestinal senescence are not fully elucidated. In this study, we initially observed a marked increase in intestinal permeability and a notable elevation in oxidative stress levels in induced senescent mice. Supplementation with CCFM8610 notably alleviated these symptoms and enhanced intestinal barrier integrity. Subsequently, analysis of different parts (3 kDa) of the CCFM8610 fermentation supernatant fractions and non-targeted metabolomics data identified indole-3-lactic acid (ILA) as a potentially critical component. ILA was found to significantly reduce elevated oxidative stress levels in senescent NCM460 cells and mitigate cellular senescence. Mechanically, ILA activated adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling, promoted nuclear Factor erythroid 2-Related Factor 2 (NRF2) nuclear expression, reduced oxidative stress, and improved cell viability, thereby alleviating intestinal senescence. These findings indicate that CCFM8610 shows significant potential in addressing intestinal senescence, with ILA identified as a key bioactive compound responsible for these effects. [Display omitted] •Lactiplantibacillus plantarum CCFM8610 could ameliorate intestinal aging by reducing oxidative stress.•Indole-3-lactic acid was the key metabolite of CCFM8610.•Indole-3-lactic acid activated the AMPK/NRF2 signaling pathway to regulate intestinal senescence.