Lactobacillus helveticus KLDS1.8701 alleviates d-galactose-induced aging by regulating Nrf-2 and gut microbiota in mice

Aging is commonly associated with chronic oxidative stress and mild inflammation that can cause a variety of degenerative diseases. Lactic acid bacteria (LAB) provide several health benefits to the host including antioxidant activity and immune system regulation. However, there is a lack of information regarding the antioxidant mechanisms of probiotics in vivo. Therefore, the aim of this study was to elucidate the possible mechanisms for the preventive effect of LAB on aging. First, 25 LAB strains were screened for finding potential probiotics with high antioxidant capacity using in vitro methods. Second, d-galactose was administered by subcutaneous injection once daily for 8 weeks to establish an aging mouse model to investigate the protective effects and underlying mechanisms of the potential probiotic strain Lactobacillus helveticus KLDS1.8701, identified from the screening. The results in vitro showed that L. helveticus KLDS1.8701 had a better property with remarkable free radical scavenging activity. In vivo, L. helveticus KLDS1.8701 supplementation significantly ameliorated aging-related changes such as decreased organic index, liver injury and increased endotoxin. L. helveticus KLDS1.8701 supplementation reduced hepatic oxidative stress by modulating the Nrf-2 pathway. Notably, L. helveticus KLDS1.8701 supplementation restored the gut microbiota composition to that of the control group, resulting in increased butyrate production and decreased endotoxin production. These findings indicated that L. helveticus KLDS1.8701 supplementation manipulated gut microbiota and its metabolites could attenuate hepatic oxidative stress via the gut-liver axis.