Lactobacillus johnsonii-derived extracellular vesicles restore mucosal immunity via taurine-linked Th17/Treg and IgA/IgG regulation in colitis

Aberrant mucosal immune responses to gut microbiota contribute to inflammatory bowel disease (IBD), yet the mechanisms linking immunoglobulin-coated bacteria to mucosal inflammation remain unclear. Microbial extracellular vesicles (EVs) have emerged as potential modulators of host–microbiota interactions, metabolism, and immunity. This study examined how Lactobacillus johnsonii-derived EVs influence gut microbiota, amino acid metabolism, mucosal T cell polarization—particularly the Th17/Treg balance—and immunoglobulin transport in experimental colitis. Flow cytometry of fecal samples from IBD patients revealed increased IgA-, IgG-, and IgM-coated bacteria. Colonic expression of PIGR and FcRn was also elevated. L. johnsonii was depleted in ulcerative colitis, whereas Proteobacteria and Escherichia_Shigella were enriched. EVs displayed high structural integrity, gastrointestinal stability, and enhanced accumulation in inflamed colon. In DSS-induced colitis mice, both L. johnsonii and EVs alleviated inflammation, improved histology, reduced pro-inflammatory cytokines, decreased Th17 cells, increased Treg cells, and restored the Th17/Treg balance. These interventions also reduced IgA-, IgG-, and IgM-coated bacteria, lowered fecal immunoglobulins without affecting systemic levels, and downregulated PIGR and FcRn. Multi-omics analyses showed that EVs reshaped gut microbiota, enriched taurine-associated taxa (Lactobacillales, Lactobacillaceae, Lactobacillus murinus), and elevated the immunoregulatory metabolite taurine, which was linked to sulfur metabolism and epithelial homeostasis. Taurine supplementation reproduced EV effects, including reduced inflammation, improved barrier integrity, Th17/Treg rebalancing, and suppression of PIGR and FcRn. L. johnsonii-derived EVs restore mucosal immune balance in colitis through a coordinated EV–taurine–Th17/Treg–PIGR/FcRn–IgA/IgG axis. By integrating microbiota remodeling, metabolic regulation, and immune modulation—and outperforming the parent bacterium in stability, colonic enrichment, and breadth of effect—these EVs represent promising next-generation biologics for IBD therapy.