Exopolysaccharides act as mediators of cross-talk between probiotics and the host. Here, we found that EPS derived from probiotic Lactobacillus casei WXD030 strain (L-EPS) could modulate immune responses in vitro and in vivo. L-EPS could significantly enhance the proliferation and phagocytic activity as well as induce the production of NO, TNF-α, IL-1β and IL-6 in RAW264.7 cells. Furthermore, L-EPS could induce the maturation of BMDCs. In addition, L-EPS could largely increase the titres of OVA-specific antibodies and markedly enhanced T cell proliferation. Notably, L-EPS also increased expression of IL-4 and INF-γ expression in CD4 + T cells. Consistently, when used as an adjuvant in vivo with the foot-and-mouth disease vaccine, L-EPS largely enhanced the FMDVspecific antibody production. Collectively, these results suggested that L-EPS derived from probiotic L. casei strain had adjuvant activity, which may be a safe and efficacious adjuvant candidate suitable for a wide spectrum of prophylactic and therapeutic vaccines.

Liver diseases alter the gut microbiota, but several lactic acid bacteria can reduce the degree of liver damage. The present study investigated whether Lactobacillus buchneri TCP016 reduces the degree of liver damage by modifying the gut microbiota via its exopolysaccharides (EPSs). First, it was illustrated that the main EPS (EPS016; molecular weight = 8.509 × 104 Da) comprised rhamnose, xylose, glucosamine, glucuronic acid, galactose, galacturonic acid, glucose, and mannose in molar ratios of 9.2:3.9:3.8:2.8:2.1:2.0:1.6:1.0. Our data showed that EPS016 alleviated the increase in plasma and hepatic enzyme and cytokine levels, increased superoxide dismutase and glutathione activity, and alleviated bacterial translocation to the liver and mesenteric lymph nodes in vivo. Furthermore, EPS016 ameliorated intestinal mucosal injury and gut flora dysbiosis, thereby decreasing the enrichment of Helicobacteraceae, Lachnospiraceae, and Enterobacteriaceae and increasing the abundance of Lactobacillus, Rikenellaceae, Bacteroidaceae, Bacteroidales_S24-7_group, and Prevotellaceae. These findings indicated that EPS016 inhibits lipopolysaccharides/d-galactosamine-induced liver injury and improves the modification of the gut microbiota.

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Staphylococcus aureus is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. S. aureus initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against S. aureus infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral S. aureus vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant Lactobacillus strains synthesizing S. aureus nontoxic mutated α-hemolysins (HlaH35L). The results from animal clinical trials showed that recombinant Lactobacillus can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant L. plantarum WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer’s patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against S. aureus pulmonary infection and significantly reduced the abscess size in a S. aureus skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered Lactobacillus WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by S. aureus. Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for S. aureus.

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