<i>Lactobacillus Johnsonii</i> RS‐7 Prevents Nrf2‐Mediated Intestinal Oxidative Damage by Modulating Microbial Metabolites

Oxidative stress is a crucial pathological basis for diverse intestinal diseases, such as inflammatory bowel disease (IBD). Previous studies show that Lactobacillus johnsonii RS-7 alleviates colitis in mice, but its effect on intestinal oxidative stress remains unclear. Considering this, the research aimed to explore the role and mechanism of this strain in alleviating oxidative damage in a colitis model. Colitis was induced in the mice using dextran sulfate sodium (DSS), and mice were subsequently randomly assigned to four groups. L. johnsonii RS-7 was evaluated for its effects on colon damage, oxidative stress, the Nrf2 pathway, and intestinal metabolites using histopathology, biochemical assays, qPCR, Western blotting, and non-targeted metabolomics. The results showed that L. johnsonii RS-7 significantly attenuated DSS-induced colonic tissue injury and reversed the DSS-associated decreases in serum CAT, T-SOD, GSH, and T-AOC levels (p < 0.05), along with an increase in malondialdehyde (MDA) (p < 0.05). Moreover, the strain significantly mitigated the down-regulation of antioxidant enzyme mRNA expression in colonic tissues (p < 0.05). Mechanistically, L. johnsonii RS-7 restored expression of Nrf2, NQO1, and HO-1 proteins in the colon and suppressed the up-regulation of Keap1. Non-targeted metabolomic analysis of intestinal contents further demonstrated that the strain significantly reduced levels of LPS 18:0 and triglycerides while concurrently increasing concentrations of DL-lysine and 5-hydroxylysine (p < 0.05). Correlation analysis indicated that LPS 18:0 and DL-lysine might be key metabolites regulating oxidative stress. The above results suggest that L. johnsonii RS-7 can alleviate colonic oxidative damage by regulating metabolites to activate the Nrf2 pathway, providing theoretical support for applying this strain to prevent intestinal diseases.