Lactobacillus Johnsonii RS-7 Prevents Nrf2-Mediated Intestinal Oxidative Damage by Modulating Microbial Metabolites

Area of Science:

• Microbiology
• Gastroenterology
• Oxidative Stress Research

Background:

• Oxidative stress is a key factor in intestinal diseases like inflammatory bowel disease (IBD).
• Lactobacillus johnsonii RS-7 has shown promise in alleviating colitis, but its impact on intestinal oxidative stress requires elucidation.

Purpose of the Study:

• To investigate the role and mechanism of Lactobacillus johnsonii RS-7 in mitigating oxidative damage in a dextran sulfate sodium (DSS)-induced colitis model.
• To explore the strain's effects on colon damage, oxidative stress markers, the Nrf2 signaling pathway, and intestinal metabolites.

Main Methods:

• Induction of colitis in mice using DSS, followed by administration of L. johnsonii RS-7.
• Assessment of colon damage via histopathology.
• Measurement of oxidative stress markers (CAT, T-SOD, GSH, T-AOC, MDA) using biochemical assays.
• Evaluation of antioxidant enzyme mRNA expression via qPCR.
• Analysis of Nrf2 pathway protein expression (Nrf2, NQO1, HO-1, Keap1) using Western blotting.
• Characterization of intestinal metabolites using non-targeted metabolomics.

Main Results:

• L. johnsonii RS-7 significantly reduced DSS-induced colonic injury and reversed alterations in serum oxidative stress markers.
• The strain mitigated the downregulation of antioxidant enzyme mRNA in colonic tissues.
• L. johnsonii RS-7 restored Nrf2 pathway protein expression while suppressing Keap1.
• Metabolomic analysis revealed modulation of specific metabolites, including reduced LPS 18:0 and triglycerides, and increased DL-lysine and 5-hydroxylysine.
• Correlation analysis suggested LPS 18:0 and DL-lysine as key metabolites involved in oxidative stress regulation.

Conclusions:

• Lactobacillus johnsonii RS-7 effectively alleviates colonic oxidative damage in a DSS-induced colitis model.
• The strain's protective mechanism involves activating the Nrf2 pathway and modulating intestinal metabolites.
• These findings provide a theoretical basis for utilizing L. johnsonii RS-7 in the prevention and treatment of intestinal diseases.