Background: Dietary intervention is the preferred approach for the prevention and clinical management of gout. Nevertheless, the existing evidence regarding the influence of specific foods on gout is insufficient. Methods: We used two-sample Mendelian randomization for genetic prediction to analyze the relationship between the intake of more than a dozen daily food items, such as pork, beef, cheese, and poultry, and dietary macronutrient intake (fat, protein, carbohydrates, and sugar) and the risk of developing gout and elevating the serum uric acid level. Inverse-variance weighted MR analyses were used as the main evaluation method, and the reliability of the results was tested by a sensitivity analysis. Results: Cheese intake was associated with lower serum uric acid levels, and tea intake (OR = 0.523, [95%CI: 0.348~0.784], p = 0.002), coffee intake (OR = 0.449, [95%CI: 0.229~0.882], p = 0.020), and dried fruit intake (OR = 0.533, [95%CI: 0.286~0.992], p = 0.047) showed a preventive effect on the risk of gouty attacks. In contrast, non-oily fish intake (β = 1.08, [95%CI: 0.24~1.92], p = 0.012) and sugar intake (β = 0.34, [95%CI: 0.03~0.64], p = 0.030) were risk factors for elevated serum uric acid levels, and alcohol intake frequency (OR = 1.422, [95%CI: 1.079~1.873], p = 0.012) was a risk factors for gout predisposition. Conclusions: These results will significantly contribute to the formulation and refinement of nutritional strategies tailored to patients afflicted with gout.

Background: Gout is a common disease with high incidence due to unhealthy diet and living habits. Simiao Powder, as a classic formula consisted of four common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism of Simiao Powder is still unclear.Methods: Based on network pharmacology, Simiao Powder active compounds were identified in TCMSP, ETCM and BATMAN database, used to establish a network of interaction between potential targets of Simiao Powder and known therapeutic targets of gout. Subsequently, the key potential targets are being used for protein–protein interaction, GO enrichment analysis and KEGG pathway enrichment analysis through several authoritative open databases. Molecular docking through AutoDockTools software can verify interaction between molecules. Finally, to validate the predicted results, in vivo experiments based on hyperuricemic-gout mice model were designed and treated with Simiao powder and allopurinol. Serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) and xanthine oxidase (XOD) were determined using a customized assay kit while the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA were analyzed through qRT-PCR.Results: Disease-target-compound network was visualized basing on the 20 bioactive compounds and the 19 potential targets using Cytoscape software. The results of PPI analysis, GO enrichment and KEGG pathway enrichment analysis indicate that the potential mechanism of Simiao Powder in treating gout may be achieved by regulating immune and inflammatory reactions, improving metabolism and endocrine. The results of molecular docking show that most of the targets and components have good binding activity. In vivo experiments revealed that Simiao powder can decreased serum UA and XOD levels in hyperuricemic-gout mice, and improved renal function. Furthermore, Simiao powder certainly regulates the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA in ankle tissue in hyperuricemic-gout mice.Conclusion: Collectively, this research predicted a multiple compounds, targets, and pathways model mechanism of Simiao Powder in the prevention and treatment of gout, providing new ideas and methods for in-depth research, via vivo experiments.

Plantago asiatica L. (PTGA) is a widely used herbal medicine for the treatment of gout and hyperuricemia (HUA). Emerging evidence highlights the pivotal role of the gut microbiota in the pathogenesis of gout and HUA. However, existing research has failed to identify and verify the key mediator strains of PTGA that exert its role in lowering uric acid. A hyperuricemia mouse model was established by intraperitoneal co-administration of hypoxanthine (100 mg/kg) combined with potassium oxonate (50 mg/kg) daily for 10 consecutive days. Serum uric acid (sUA) levels and renal function parameters were assessed using biochemical assay kits. 16S rRNA sequencing combined with non-targeted metabolomics was employed to characterize alterations in gut microbiota and intestinal metabolites. Western blotting was performed to examine the expression of intestinal and renal uric acid transporters, intestinal tight junction proteins, and NLRP3 inflammasome-related proteins. Finally, the mediate role of gut microbiota was verified through fecal microbiota transplantation (FMT) and oral supplementation with Lachnospiraceae bacterium. In the HUA model, elevated sUA levels (p < 0.01), activation of the renal NLRP3 inflammasome (p < 0.05), renal edema, and impaired renal function were accompanied by gut microbiota dysbiosis. PTGA extract markedly reduced sUA levels by approximately 70 % compared to the model group (p < 0.01), regulated uric acid transporter expression in both the intestine and kidney (p < 0.05), and reshaped gut microbiota composition. Moreover, PTGA enhanced intestinal uric acid catabolism of uric acid in the intestine. FMT and Lachnospiraceae bacterium supplementation experiments further confirmed the regulation of the gut microbiota is a key mediator of PTGA's therapeutic efficacy. This study demonstrates that PTGA exerts hypouricemic and renoprotective effects through modulation of the gut-kidney axis by enriching Lachnospiraceae, promoting intestinal uric acid catabolism, and suppressing renal NLRP3 inflammasome activation. These findings provide novel mechanistic insights into the gut microbiota-dependent therapeutic action of herbal medicine, distinguishing this work from previous studies focused solely on direct organ-level effects.

Aim. The prevalenceof nonalcoholic fatty liver disease (NAFLD)is increasing worldwide, but there are currently limited treatmentoptions available. Therefore, it is necessary to research new treatmentstrategies. Zhuyu Pill (ZYP) is a well-known herbal recipe consistingof Huanglian (Coptidis rhizoma) and Wuzhuyu (Evodiae Fructus) thathas been clinically used to treat NAFLD. This study aimed to investigatethe impact of ZYP on NAFLD induced by a high-fat diet (HFD) and toidentify its potential mechanism. Methods. In this investigation,we used ZYP to treat a mouse model of NAFLD induced by an HFD. Weconducted various analyses including assessment of serum biochemicalindices, histological evaluation, fecal metabonomics analysis, westernblot, and quantitative real-time polymerase chain reaction. Results.ZYP effectively improved blood lipid levels and reduced inflammatoryresponse in HFD mice, while also alleviating liver cell damage andlipid accumulation. Additionally, ZYP influenced the fecal bile acid(BA) metabolism profiles of HFD mice by inhibiting the signal transductionof ileal farnesoid X receptor (FXR) fibroblast growth factor 15 (FGF15),enhancing the expression of cytochrome P450 family 7 subfamily A member1(CYP7A1), promoting BA synthesis and increasing the metabolic eliminationof cholesterol. Conclusion. ZYP shows promise as a potential treatmentfor alleviating NAFLD by modulating BA metabolism through the FXR-FGF15-CYP7A1pathway.

The communication mechanism of the gut–lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not in close proximity to each other. However, the specific communication mechanism involving gut microbiota, immune cells, and their anti-influenza effects in the lung remains to be further elucidated. In this study, the effects of 731 species of peripheral immune cells and 211 different gut microbiota on influenza outcomes were analyzed using a two-sample Mendelian randomization analysis. After identifying specific species of gut microbiota and peripheral immune cells associated with influenza outcomes, mediation analyses were conducted to determine the mediating effects of specific immune cells in the protective or injurious effects of influenza mediated by gut microbiota. 19 species of gut microbiota and 75 types of peripheral immune cells were identified as being associated with influenza susceptibility. After rigorous screening, 12 combinations were analyzed for mediated effects. Notably, the down-regulation of CD64 on CD14- CD16- cells mediated 21.10% and 18.55% of the protective effect of Alcaligenaceae and Dorea against influenza, respectively. In conclusion, focusing on influenza, this study genetically inferred different types of gut microbiota and peripheral immune cells to determine their protective or risk factors. Furthermore, mediation analysis was used to determine the proportion of mediating effects of peripheral immune cells in gut microbiota-mediated susceptibility to influenza. This helps elucidate the gut–lung axis mechanism by which gut microbiota affects influenza susceptibility from the perspective of regulation of peripheral immune cells.

Background: Pingwei Powder (PWP), a renowned traditional Chinese medicine (TCM) formula, it has demonstrated excellent therapeutic effects in ulcerative colitis (UC), yet its underlying pharmacological mechanisms remain unclear. This study aims to investigate the therapeutic effect of PWP on the aggravation of colonic inflammation induced by a high-fat diet and particularly focuses on its regulatory mechanisms on gut microbiota, which are closely related to UC.Methods: Network pharmacology analysis was employed to screen potential pharmacological targets of PWP for UC. Histological changes in colonic tissue were observed using hematoxylin and eosin (H&E) staining, and immunofluorescence staining was performed to evaluate the expression of tight junction proteins (ZO1 and Occludin). Western blotting was used to detect the expression levels of proteins related to the PI3K/AKT/mTOR pathway, ZO1, and Occludin. qRT-PCR was conducted to measure the relative expression of inflammatory cytokines (IL-1β, IL-17, IL-6, and TNF-α) in colonic tissue. Additionally, 16S rDNA sequencing was performed to analyze gut microbiota alterations, and GC/MS was used to quantify short-chain fatty acids (SCFAs) in gut contents. The gutMgene database was utilized to validate the mediating roles of gut microbiota metabolites in the pharmacological effects of PWP. And their mediating role in PWP efficacy was verified by fecal microbiota transplantation (FMT) and butyrate supplementation.Results: Network pharmacology analysis predicted that PWP may regulate the PI3K/AKT pathway to exert therapeutic effects in UC. Experimental validation showed that PWP significantly downregulated the levels of PI3K, pAKT/AKT, and pmTOR/mTOR in colonic tissue, thereby enhancing autophagy in colonic epithelial cells, as evidenced by decreased levels of P62 and increased LC3B-II/LC3B-I ratios. Furthermore, 16S rDNA sequencing combined with targeted SCFAs analysis of gut contents revealed that the pharmacological effects of PWP may be mediated by increasing the abundance of SCFAs-producing gut microbiota (Alistipes and Parabacteroides) and elevating the levels of SCFAs in the gut.Conclusion: PWP enhances the abundance of SCFAs-producing bacteria (Alistipes and Parabacteroides) in the gut, increases the levels of butyrate, and inhibits the PI3K/AKT/mTOR pathway in the colon. These effects promote colonic autophagy and contribute to the resolution of colonic inflammation.