Commensal bacteria modulate acute immune responses to infection in hosts. In this study, Enterococcus faecium C171 was screened and isolated. This strain has similar basic characteristics to the reference probiotic, including strong anti-inflammatory and anti-infective effects. E. faecium C171 inhibits the production of pro-Caspase-1 and significantly reduces the production of interleukin-1β (IL-1β) in vitro. These reactions were confirmed using the Transwell system. Live E. faecium C171 mainly exerted an inhibitory effect on acute inflammation, whereas the anti-infective and immune-activating effects were primarily mediated by the E. faecium C171-produced bacterial extracellular vesicles (Efm-C171-BEVs). Furthermore, in the specific pathogen-free (SPF) chicken model, oral administration of E. faecium C171 increased the relative abundance of beneficial microbiota (Enterococcus and Lactobacillus), particularly Enterococcus, the most important functional bacteria of the gut microbiota. E. faecium C171 significantly inhibited the acute inflammatory response induced by a highly virulent infectious disease, and reduced mortality in SPF chickens by 75%. In addition, E. faecium C171 induced high levels of CD3⁺_, CD4^-, and CD8^- immunoregulatory cells and CD8⁺ killer T cells, and significantly improved the proliferative activity of T cells in peripheral blood mononuclear cells, and the secretion of interferon-γ. These findings indicate that E. faecium C171 and Efm-C171-BEVs are promising candidates for adjuvant treatment of acute inflammatory diseases and acute viral infections.

Recent reports of infectious bursal disease virus (IBDV) infections in China, Japan, and North America have indicated the presence of variant, and the current conventional IBDV vaccine cannot completely protect against variant IBDV. In this study, we constructed recombinant Lactococcus lactis (r-L. lactis) expressing a novel variant of IBDV VP2 (avVP2) protein along with the Salmonella resistance to complement killing (RCK) protein, and Western blotting analysis confirmed that r-L. lactis successfully expressed avVP2-RCK fusion protein. We immunized chickens with this vaccine and subsequently challenged them with the very virulent IBDV (vvIBDV) and a novel variant wild IBDV (avIBDV) to evaluate the immune effect of the vaccine. The results show that the r-L. lactis-avVP2-RCK-immunized group exhibited a 100% protection rate when challenged with avIBDV and 100% survival rate to vvIBDV. Furthermore, this immunization resulted in the production of unique neutralizing antibodies that cannot be detected by conventional ELISA. These results indicate that r-L. lactis-avVP2-RCK is a promising candidate vaccine against IBDV infections, which can produce unique neutralizing antibodies that cannot be produced by other vaccines and protect against IBDV infection, especially against the variant strain.

Background/Objectives: To investigate the antagonistic effect of probiotic Lactiplantibacillus plantarum GUANKE against respiratory syncytial virus (RSV) and its underlying molecular mechanisms. Methods: in vitro cell models (A549 and HEp2 cells) and an in vivo mouse model (BALB/c mice) were employed. RT-qPCR, TCID50 assay, immunofluorescence, ELISA, Western blot, and histopathological analysis were used to investigate the effects of GUANKE on RSV replication, inflammatory responses, and the type I interferon pathway. Results: Oral administration of GUANKE effectively cleared RSV and alleviated RSV-induced pulmonary inflammatory responses. GUANKE inhibited viral replication. The GUANKE intervention group exhibited significantly reduced pathological damage to lung tissue and decreased the expression of inflammatory cytokines (IL-1β, IL-6, MCP-1, TNF-α). GUANKE augmented the early type I interferon response and activated the STING-TBK1-IRF3-IFN signaling pathway. Conclusions: GUANKE exerts anti-RSV effects by enhancing the early type I interferon response and activating the STING-TBK1-IRF3-IFN signaling pathway, thereby inhibiting RSV replication and alleviating pulmonary inflammatory responses. This suggests its potential value as an anti-RSV agent.

Klebsiella pneumoniae (KP) is an important opportunistic pathogen that can persist in the gastrointestinal tract and serve as a reservoir for subsequent infection. The increasing prevalence of multidrug-resistant KP highlights the need for non-antibiotic strategies to limit intestinal KP burden and associated host injury. Lactiplantibacillus plantarum GUANKE (L. plantarum GUANKE) is a candidate probiotic strain with reported effects on mucosal barrier protection and inflammatory regulation, but its role in intestinal KP challenge remains unclear. In this study, the effects of L. plantarum GUANKE and its metabolite phenyllactic acid (PLA) on KP growth, intestinal KP burden, and associated inflammatory injury were investigated using antibacterial assays in vitro, metabolomic analyses, an antibiotic-pretreated mouse model of intestinal KP challenge, and an influenza A virus (IAV)/KP intestinal co-exposure model. L. plantarum GUANKE and its culture-derived products inhibited KP growth in vitro. Metabolomic analysis identified PLA as a metabolite enriched in L. plantarum GUANKE fermentation supernatants, and exogenous PLA directly inhibited KP growth in a dose-dependent manner. In an antibiotic-pretreated mouse model of intestinal KP challenge, oral administration of L. plantarum GUANKE reduced intestinal KP burden and was associated with changes in gut microbiota composition, increased cecal PLA abundance, improved intestinal barrier-related parameters, and reduced inflammatory responses, while exogenous PLA partially reproduced these effects. IAV infection increased susceptibility to intestinal KP expansion, and oral L. plantarum GUANKE reduced KP burden in the IAV/KP intestinal co-exposure model. In mice challenged with multidrug-resistant KP strain NK04152, L. plantarum GUANKE and PLA reduce intestinal KP burden and associated tissue injury in mice, supporting their potential as candidate microbiota and metabolite strategies against intestinal KP challenge.

Background: The global prevalence of hyperuricemia (HUA) has increased worldwide, and probiotics are considered an adjunctive treatment with fewer side effects. However, the effective strains and underlying mechanisms are not well understood. Objective: This study aimed to investigate the role of Lacticaseibacillus paracasei SUB12 (SUB12) in alleviating HUA and elucidate its potential molecular mechanisms. Methods: In this study, a HUA mouse model was established using potassium oxonate and adenine to evaluate the uric acid-lowering effect of SUB12. High-throughput metabolomics and 16S rRNA sequencing were used to identify key metabolites and altered microbiota. Results: Oral administration of SUB12 significantly reduced serum UA level, hepatic xanthine oxidase (XOD) activity, and renal inflammation and altered uric acid transport-related proteins. Sequencing analysis suggested that SUB12 not only had the capacity of consuming succinate but also reduced the abundance of succinate-producing Prevotellamassilia. Succinate supplementation significantly promoted XOD activity through the succinate receptor 1 (SUCNR1)/hypoxia-inducible factor 1-alpha (HIF-1α) axis. Conclusions: Our findings reveal that SUB12 attenuates hyperuricemia by down-regulating succinate, which promotes XOD activity and uric acid production through the SUCNR1/HIF-1α/XOD axis.