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 d...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 and>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.展开更多
基金supported by the National Natural Science Foun-dation of China(32272290 and 31972973)the Fundamental Research Funds for the Central Universities(JUSRP22004).
文摘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 and>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.
