Extracellular Vesicles From Lactobacillus fermentum Enhance Intestinal Barrier Integrity and Restore Gut Microbial Homeostasis in Experimental Murine Colitis

Background

Lactobacillus fermentum has been shown to improve intestinal health and treat colitis; however, its precise efficacy and mechanisms in inflammatory bowel disease 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 6 groups: control, 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 1-wk acclimation, mice were gavaged daily for 3 wk. Fresh cultures, including live (LF+DSS), heat-inactivated (LHF+DSS), supernatant (LSF+DSS), and extracellular vesicles (LEV+DSS), were prepared daily. During the final 7 d, the control group received normal water, and the other groups received 3% DSS. Data were collected daily, followed by sample collection from the mice.

Results

In this study, significant reductions (P < 0.05) in body weight changes, disease activity index, 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, whereas proinflammatory cytokines IL-1β and 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. Linear discriminant analysis effect size analysis revealed an enrichment of beneficial bacteria including Prevotellaceae_UCG-001, Romboutsia, and Ruminococcus species in the LF+DSS group and Akkermansia, Odoribacter, and Marvinbryantia species in the LEV+DSS group. Both L fermentum and its extracellular vesicles significantly downregulated the gene expression of TNF-α and IL-1β, whereas the expression of IL-10 was upregulated, 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.