Lactobacillus Plantarum NC8 and its metabolite acetate alleviate type 1 diabetes via inhibiting NLRP3.

A healthy organism is the result of host-microbiome co-evolution. Microbial metabolites can also stimulate immune cells to reduce intestinal inflammation and permeability. Gut dysbiosis will lead to a variety of autoimmune diseases, such as Type 1 diabetes (T1D). Most of probiotics, such as Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidium, and Streptococcus thermophiles, can improve the intestinal flora structure of the host, reduce intestinal permeability, and relieve symptoms of T1D patients if ingested above probiotics in sufficient amounts. Lactobacillus Plantarum NC8, a kind of Lactobacillus, whether it has an effect on T1D, and the mechanism of it regulating T1D is still unclear. As a member of the inflammatory family, NLRP3 inflammasome can enhance inflammatory responses by promoting the production and secretion of proinflammatory cytokines. Many previous studies had shown that NLRP3 also plays an important role in the development of T1D. When the NLRP3 gene is deleted, the disease progression of T1D will be delayed. Therefore, this study investigated whether Lactobacillus Plantarum NC8 can alleviate T1D by regulating NLRP3. The results demonstrated that Lactobacillus Plantarum NC8 and its metabolites acetate play a role in T1D by co-modulating NLRP3. Lactobacillus Plantarum NC8 and acetate can reduce the damage of T1D in the model mice, even if orally administered them in the early stage of T1D. The number of Th1/Th17 cells in the spleen and pancreatic lymph nodes (PLNs) of T1D mice were significantly reduced by oral Lactobacillus Plantarum NC8 or acetate. The expression of NLRP3 in the pancreas of T1D mice or murine macrophages of inflammatory model were significantly inhibited by treatment with Lactobacillus Plantarum NC8 or acetate. In addition, the number of macrophages in the pancreas were significantly reduced by the treatment with Lactobacillus Plantarum NC8 or acetate. In summary, this study indicated that the regulatory mechanism of Lactobacillus Plantarum NC8 and its metabolite acetate to T1D maybe via inhibiting NLRP3 and provides a novel insights into the mechanism of the alleviated role of probiotics to T1D.

Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets.

BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

Lactobacillus plantarum Surface-Displayed ASFV (p14.5) Can Stimulate Immune Responses in Mice.

African Swine Fever Virus (ASFV) has spread worldwide, and the lack of vaccines severely negatively impacts the pig industry. In this study, the p14.5 protein encoded by ASFV was used as the antigen, and the p14.5 gene was expressed in vitro using the Lactobacillus expression system. Three new functionally recombinant Lactobacillus plantarum (L. plantarum) were constructed and the expressions of the p14.5 protein, p14.5-IL-33-Mus fusion protein and CTA1-p14.5-D-D fusion protein were successfully detected using Western blot analysis. After oral immunization of SPF mice with recombinant L. plantarum, flow cytometry and ELISA were performed to detect the differentiation and maturity of T lymphocytes, B lymphocytes and DCs of the mice, which were higher than those of the control group. Specific antibodies were produced. The immunogenicity of the adjuvant group was stronger than that of the single antigen group, and the IL-33 adjuvant effect was stronger than that of the CTA1-DD adjuvant.

Gut Bacterial Composition and Functional Potential of Tibetan Pigs Under Semi-Grazing.

Gut bacterial community plays a key role in maintaining host health. The Tibetan pig (Sus scrofa), an ancient breed in China, has been known for its high adaptability to harsh environments and for its meat quality. To understand the underlying mechanisms facilitating to shape these unique features, in this study, 16S rRNA sequencing using pigs feces and subsequent bacterial functional prediction were performed. Also, the gut bacteria of two other breeds of pigs, Barkshire and Landrace, were examined for comparison. It was revealed that the structure of bacterial community in Tibetan pigs appeared to be more complex; the relative abundances of dominant bacterial families varied inversely with those of the other pigs, and the proportion of Firmicutes in Tibetan pigs was lower, but Bacteroides, Fibrobacterota, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae were higher. Bacterial functional prediction revealed that the dominant flora in the Tibetan pigs was more correlated with functions regulating the hosts' immune and inflammatory responses, such as NOD-like_receptor_signaling_pathway and vitamin metabolism. In addition, in Tibetan pigs, the taxonomic relationships in the gut bacteria on day 350 were closer than those on earlier stages. Furthermore, gender played a role in the composition and function of bacterial inhabitants in the gut; for boars, they were more correlated to drug resistance and xenobiotics metabolism of the host compared to the sows. In sum, our preliminary study on the gut bacterial composition of the Tibetan pigs provided an insight into the underlying host-microorganism interactions, emphasizing the role of intestinal bacteria in the context of modulating the host's immune system and host development.