Liqiong Song

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.

Background: Douzhier, a traditional Chinese fermented food with a history spanning over 1000 years, harbors a complex community of beneficial microbiota. In this study, we isolated Lactococcus lactis subsp. cremoris (designated L. cremoris D2022), one of the dominant bacterial species in Douzhier, and evaluated its efficacy against influenza A virus (IAV) infection. Methods: A murine model of IAV infection was established using C57BL/6J mice. Following oral administration of L. cremoris D2022, treated and model control groups (IAV-infected model control group received phosphate-buffered saline (PBS)) were comparatively assessed through clinical outcomes (body weight dynamics and survival), pathological parameters (colon length, lung index, and lung histopathology), inflammatory cytokine profiling, multi-omics analyses (lung transcriptomics and cecal metabolomics), and adaptive immune responses. Results: Administration of L. cremoris D2022 markedly alleviated IAV-induced pathology compared with PBS-treated model controls, as evidenced by improved survival (30% vs. 0%, p = 0.006), reduced body weight loss, decreased lung index, and preservation of colon length. D2022 treatment accelerated viral clearance, accompanied by enhanced early interferon beta (IFN-β) production. This was followed by suppression of late-stage hyperinflammation, including reduced levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) at 7 dpi. Metabolomic analysis revealed increased levels of deaminotyrosine (DAT), short-chain fatty acids (SCFAs), and microbially conjugated bile acids (e.g., ursodeoxycholic acid (UDCA) and isoallolithocholic acid (isoalloLCA)). Furthermore, IAV-specific adaptive immune responses were significantly enhanced. Conclusions: L. cremoris D2022 protects mice against IAV infection, with enhanced early IFN-β responses, reduced late-stage inflammation, and associated changes in intestinal microbial metabolites. The causal roles of these metabolites remain to be established. These findings support further evaluation of D2022 as a probiotic candidate for adjunctive influenza prevention.

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: Kai-Bi-Bu-Fei Decoction (KBD) is derived from the canonical Traditional Chinese Medicine formulas Xuan-Bai-Cheng-Qi and Ma-Xing-Shi-Gan. It has been employed for decades in the treatment of severe pneumonia with significant clinical efficacy. This study aimed to evaluate the protective effects of KBD against influenza virus-induced severe pneumonia in a murine model and to elucidate the underlying molecular mechanisms. Methods: The chemical profile of KBD was characterized using UPLC-Q-TOF-MS. A severe pneumonia model was established in C57BL/6J mice via intranasal infection with influenza A/Puerto Rico/8/34 (H1N1, PR8). Multiple parameters, including 14-day survival rate, body weight, lung index, histopathological changes, viral load, and pulmonary cytokine/chemokine levels, were assessed. Furthermore, multi-omics analyses were integrated to characterize the gut microbiota and metabolic profiles. Fecal microbiota transplantation (FMT) was subsequently performed to validate the functional role of the gut microbiota and its metabolites. Results: KBD treatment significantly improved the survival rate by 40%, reduced the lung index by 27.85%, and alleviated lung injury. It also markedly lowered the viral load by 80.88%, suppressed pro-inflammatory cytokine levels, and restored intestinal barrier integrity. Mechanistically, KBD restored gut microbiota diversity by increasing the abundance of Firmicutes and Bacteroidetes, enriching beneficial genera such as Bifidobacterium and Faecalibaculum, and reducing Verrucomicrobiota. Integrated transcriptomic and metabolomic analyses revealed that KBD enhanced short-chain fatty acid (SCFA) metabolism and up-regulated pyruvate metabolism. Finally, FMT confirmed that the therapeutic benefits of KBD were transferable via the microbiota to microbiota-depleted mice. Conclusions: KBD exerts robust protection against severe influenza pneumonia, a process primarily mediated by the gut microbiota–SCFA axis. The enhancement of mitochondrial energy metabolism also appears to play a critical role in its therapeutic mechanism.

Background: Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut–lung axis. While Latilactobacillus curvatus is a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood. Objective: In this study, we investigated the protective effects and underlying mechanisms of L. curvatus IM01 in an ovalbumin (OVA)-induced murine AAI model using an integrated multi-omics approach. Results: Our results demonstrated that oral administration of L. curvatus IM01 significantly attenuated airway inflammation, suppressed Th2-type immune responses, and reduced serum IgE levels. Crucially, our multi-omics integration revealed a coherent gut–lung axis narrative driven by microbial and metabolic crosstalk. Specifically, 16S rRNA sequencing indicated that L. curvatus IM01 was closely linked to structural shifts in the gut microbial community, notably characterized by an enrichment trend for beneficial genera such as Odoribacter and Lactobacillus. This microbial restructuring was closely associated with a modulated cecal metabolic profile, as untargeted metabolomics exhibited a clear trend toward the restoration of key systemically active immunoregulatory metabolites, including indolelactic acid (ILA) and choline, which have been previously linked to the alleviation of AAI symptoms. Further linking this metabolic shift to respiratory immune tolerance, lung transcriptomic analysis showed that the treatment is strongly associated with the promotion of the differentiation of CD4⁺ T cells into Foxp3⁺ regulatory T cells (Tregs). Conclusions: Collectively, these findings suggest a novel potential pathway by which L. curvatus IM01 modulates the gut–lung axis through coordinated microbial and metabolic interventions, highlighting its potential as a therapeutic functional food ingredient for AAI.

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.

Background: Kugan granules (KGKL), a Chinese patent medicine, was used widely for the treatment of influenza in China and have demonstrated good efficacy. However, the underlying mechanism remains unclear. Objective: To investigate the anti-influenza efficacy of KGKL and to explore its mechanism of action. Materials and methods: Six-week-old C57BL/6J mice were divided into 3 groups: the blank group (control group), the infection group (model group), and the Kugan granules group (KGKL group). The latter 2 groups were administered either nonlethal or lethal doses of the influenza virus AH1N1 PR8. Tissue specimens, including those from the lungs and colon, were collected on days 1, 3, 7, and 14 postinfection (pi). The levels of IFN-β were measured on days 1 and 3 pi using ELISA, while the mRNA of interferon-related proteins was analyzed on day 1 pi using real-time polymerase chain reaction (PCR). The viral load in the lungs was quantified on days 3 and 7 pi using real-time PCR. On day 7 pi, the lung index and colon length were measured, and pathologic examinations of the lungs were conducted. In addition, multiple cytokines (IL-6, IL-1β, TNF-α, IFN-γ, CXCL-10, TGF-β, IL-4, and IL-10) in the lungs were assessed using ELISA. The expression levels of NLRP3 inflammasome-related proteins and tight junction proteins in the lungs were evaluated using Western blotting. Mouse survival was continuously monitored until day 14 pi. Results: The KGKL group exhibited significantly improved lung index (PPPPPP PPPPPP<0.05). Conclusions: The primary mechanism of KGKL anti-influenza probably involved reducing viral load by directly inhibiting virus replication or inducing IFN-I in the early stage of the infection and suppressing excessive inflammatory response by down-regulating NLRP3-Caspase1-mediated pyroptosis in the late stage of the infection.

Background/Objectives: Gut microbiota is essential for maintaining host immune homeostasis and has been confirmed to be closely related to some intestinal and extraintestinal diseases. Bacteroides, as the dominant bacterial genus in the human gut, has attracted great attention due to its excellent metabolic activity, but there are few studies on Bacteroides dorei species. In our previous study, a gut commensal strain, Bacteroides dorei RX2020 (B. dorei), was isolated from healthy human feces and exhibited superior flavonoid metabolic activity, prompting further analysis of its uncharacterized genomic features, probiotic potential, safety, and immunomodulatory activity. Results: The results showed that B. dorei exhibited intrinsic probiotic functionalities with preserved genomic and phenotypic stability, demonstrated safety profiles in murine models through in vivo assessments, and conferred antagonistic activity against enteric foodborne pathogens via competitive exclusion. The strain also demonstrated abundant metabolic activity and was involved in the metabolism of tryptophan and bile acids (BAs). Moreover, B. dorei can promote the production of IFNβ by dendritic cells (DCs) to inhibit the replication of influenza virus in epithelial cells, which may be achieved by regulating host metabolism. Conclusions: This study reveals the potential of B. dorei as next-generation probiotics (NGPs), contributing to a broader understanding and application of these novel probiotics in health and disease management.

Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have demonstrated that oral administration with probiotics may increase the immune response to lung infection via the gut-lung axis leading to the alleviation of the pulmonary disease. In this study, we evaluated the effects of oral administration of Pediococcus pentosaceus MIANGUAN2 (MIANGUAN2) on influenza infection in a mouse model. Our results showed that oral administration of MIANGUAN2 significantly improved weight loss, lung index, and lung pathology, and decreased lung viral load of influenza-infected mice. Additionally, MIANGUAN2-treated mice showed significantly lower levels of TNF-α, IL-1β, IFN-γ, and IL-12p70 and higher production of IL-4 in the lung. In accordance with this, the transcriptome analysis of the lung indicated that MIANGUAN2-treated mice had reduced expression of inflammation markers, such as TNF, apoptosis, and the NF-Kappa B pathway. Furthermore, the administration of MIANGUAN2 restored the SCFAs profiles through regulating the gut microbiota. SCFA-producing bacteria, such as p_Firmicutes, f_Lachnospiraceae, and f_Ruminococcaceae, were enriched in the MIANGUAN2-treated group compared with PBS-treated group. Consistently, the concentrations of SCFAs in the MIANGUAN2 group were significantly higher than those in the PBS-treated group. In addition, the concentrations of SCFAs were positively correlated with SCFA-producing bacteria, such as Ruminococcus, while being negatively correlated with the virial titers and proinflammatory cytokines. In conclusion, this animal study suggests that Pediococcus pentosaceus MIANGUAN2 may alleviate the influenza infection by altering the gut microbiota composition and increasing the levels of gut microbiota-derived SCFAs.