Extracellular vesicles from Lactobacillus fermentum enhance intestinal barrier integrity and restore gut microbial homeostasis in experimental murine colitis.

Background: Lactobacillus fermentum (L. fermentum) has been shown to improve intestinal health and treat colitis; however, its precise efficacy and mechanisms in inflammatory bowel disease (IBD) remain unclear.

Objectives: This study aimed to evaluate whether L. fermentum and its metabolites, extracellular vesicles, and other components could modulate intestinal barrier function and gut microbiota to alleviate dextran sulfate sodium (DSS)-induced colitis in mice.

Methods: Forty-eight mice were randomly assigned to six groups: Control (CON), DSS, L. fermentum + DSS group (LF + DSS), heat-inactivated L. fermentum + DSS group (LHF + DSS), L. fermentum supernatant solution + DSS group (LSF + DSS), and L. fermentum extracellular vesicles + DSS group (LEV + DSS). After a one-week acclimation, mice were gavaged daily for three weeks. Fresh cultures, including live (LF + DSS), heat-inactivated (LHF + DSS), supernatant (LSF + DSS), and extracellular vesicles (LEV + DSS), were prepared daily. During the final seven days, the control group received normal water, while the other groups received 3% DSS. Data were collected daily, followed by sample collection from the mice.

Results: Herein, significant reductions (P < 0.05) in body weight changes, disease activity index (DAI), intestinal damage, and histology scores were observed in the treatment groups, especially LEV + DSS and LF + DSS. Additionally, compared with the DSS group, colonic mucus secretion, as well as claudin-1 and occludin expression, increased significantly (P < 0.05) in the LEV + DSS and LF + DSS groups, while proinflammatory cytokines interleukin (IL) -1β and tumor necrosis factor-α (TNF-α) decreased (P < 0.05) and IL-10 increased (P < 0.05) in the LEV + DSS group. L. fermentum and its components significantly regulated gut microbiota α-diversity and β-diversity, affecting overall composition. LEfSe analysis revealed an enrichment of beneficial bacteria including Prevotellaceae_UCG-001, Romboutsia, and Ruminococcus in the LF + DSS group, and Akkermansia, Odoribacter, and Marvinbryantia in the LEV + DSS group. Both L. fermentum and its extracellular vesicles significantly downregulated the gene expression of TNF-α and IL-1β, while upregulating the expression of IL-10, thereby contributing to the alleviation of colitis symptoms.

Conclusions: This study reveals that L. fermentum alleviates colitis through modulation of the gut microbiota and reinforcement of the intestinal mucosal barrier, with its extracellular vesicles potentially playing a key role in this regulatory process.