Hyperuricaemia (HUA) is a disorder of purine metabolism, which manifests itself as an increase in uric acid production and a decrease in uric acid excretion, as well as a change in the structure of the intestinal microbiota. Most of the drugs currently used to treat HUA have significant side effects, and it is essential to find a treatment for HUA that is free of side effects. In this study, a novel strain, Pediococcus acidilactici GQ01, was screened from natural fermented wolfberry. The effects of both live bacteria GQ01 and its heat-killed G1PB postbiotic on HUA were investigated. The results showed that both probiotic GQ01 and G1PB postbiotics could effectively decrease blood uric acid, creatinine, and urea nitrogen levels in the HUA mice model. P. acidilactici GQ01 was more effective in inhibiting ADA activity, while G1PB postbiotics was more effective in inhibiting XOD activity. Meanwhile, GQ01 and G1PB were able to ameliorate liver and kidney tissue injury, upregulate the expression of ABCG2 in kidney and XOD gene in liver, downregulate the protein expression of URAT1 and GLUT9 in kidney, and therefore reduce the value of blood uric acid by decreasing the uric acid reabsorption and increasing the excretion of uric acid. Additionally, both probiotics and postbiotics could regulate the intestinal microbiota structure of HUA mice, so as to bring the dysfunctional intestinal composition back to normal. Furthermore, P. acidilactici GQ01 and G1PB postbiotics can increase the levels of acetic acid, propionic acid, and butyric acid in the intestinal tract, improve the intestinal function, and maintain the healthy homeostatic state of the intestinal tract. In summary, P. acidilactici GQ01 and its G1PB postbiotics may be developed as functional food or drug materials capable of treating HUA.

Alcoholic liver disease is one of the diseases with a high mortality rate worldwide, resulting from excessive and chronic alcohol consumption. With the rapid rise of intestinal microbial research, more and more researchers have begun to focus on the role of probiotics in preventing, alleviating or treating diseases. In this study, effects of lactic acid bacteria (LAB), a general type of probiotic, isolated from the fermented grains of Chinese baijiu, on alcohol-induced liver injury and alcohol metabolism were investigated, and the results showed that Lactiplantibacillus pentosus LTJ12, Pediococcus acidilactici LTJ28, Lactiplantibacillus plantarum LTJ30, and Pediococcus acidilactici LTJ32 could prevent drunkenness and sober up, and had a good protective effect on alcoholic liver injury. These LAB, especially Lactiplantibacillus, can reduce the drunken rate and mortality of drinking mice, shorten the sobriety time, decrease the content of ethanol in serum, reduce the activity or content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglyceride (TG) and malondialdehyde (MDA), increase the activity or content of superoxide dismutase (SOD), glutathione (GSH) and nitric oxide (NO), and also improve the activity of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) of the liver. The LAB intervention basically reversed the changes in the mRNA levels of genes related to ethanol/drug metabolism (CYP2E1, ADH1 and ALDH2), antioxidant markers (SOD2 and CAT), cellular inflammation, apoptosis and proliferation (SIRT1, SMYD3 and BRD4) and lipid metabolism (SREBP1 and FASn). In addition, we have found that the regulatory effect of these probiotics may be related to the SMYD3/BRD4 pathway, which needs further detailed research. Besides, the probiotics increased the abundance of gut microbes, restored the imbalance of the intestinal flora caused by alcohol consumption, and regulated the changes in the intestinal short-chain fatty acid content caused by chronic alcohol consumption. These results suggested that these baijiu-derived probiotics can effectively prevent drunkenness and chronic alcoholic liver injury. It is of great significance to provide scientific basis for subsequent research and development of new anti-alcoholism health products based on probiotics and the intestinal microecological regulation mechanism.

Objectives: Hyperuricemia (HUA) is a metabolic disorder linked to serious complications, yet current treatments face safety limitations. This study aimed to identify novel probiotic strains from Chinese Baijiu fermentation grains with dual-action mechanisms for HUA management—direct uric acid (UA) reduction and gut microbiota restoration. Methods: Two Lactiplantibacillus plantarum strains (LTJ1/LTJ48) were screened for purine/nucleoside degradation using HPLC. Their efficacy was evaluated in HepG2 cells and HUA mice. Key assessments included UA levels, renal/hepatic markers (AST, CRE, BUN), ADA/XOD activity, UA transporter expression (URAT1, GLUT9, ABCG2), and 16S rRNA-based microbiota analysis. Results: LTJ1/LTJ48 degraded >97% of purines/nucleosides in vitro. In HUA mice, they reduced serum UA by 31.0% (LTJ1) and 51.5% (LTJ48), improved renal/hepatic function, and suppressed ADA activity. They modulated UA transporters and restored gut microbiota. Conclusions: LTJ1/LTJ48 exhibit multi-target HUA alleviation via purine degradation, ADA inhibition, UA transporter regulation, and microbiota remodeling, offering a safer probiotic-based alternative to conventional therapies. Their translational potential warrants further clinical exploration.

Hyperuricemia (HUA) is a metabolic disorder characterized by excessive uric acid (UA) production and impaired excretion. Goji, as a representative medicinal food, holds significant research and development value, while probiotic fermentation technology is finding increasingly widespread applications in the functional food sector. This study developed a novel goji fermented with three probiotic strains (Lactoplantibacillus plantarum CGMCC8198, Lactococcus lactis LTJ28, and Lactocaseibacillus casei YR2-2) and investigated its anti-HUA effects. Optimal fermentation conditions (7.913 material–liquid ratio, 3.92% inoculation, 7.49 h at 37 °C with 1:1:2 strain ratio) yielded a beverage with enhanced flavor profiles (19 aroma compounds) and high viable counts. In HUA cell models, the 15% fermented goji juice significantly reduced UA levels by 56% (p < 0.01). In potassium oxonate-induced HUA mice, the beverage effectively lowered serum UA, xanthine oxidase activity, and renal function markers (blood urea nitrogen and creatinine, p < 0.0001) while improving hepatic parameters (alanine aminotransferase, aspartate Aminotransferase). The goji-fermented juice significantly reduced the expression of renal UA transporters GLUT9 and URAT1 (p < 0.0001) while improving gut microbiota composition, as evidenced by increased beneficial SCFAs (acetic acid, butyric acid, p < 0.0001) and elevated Lactobacillus abundance 2.14-fold. Our findings demonstrate that this triple-probiotic-fermented goji beverage represents an effective dietary strategy for HUA management by simultaneously inhibiting UA production, enhancing excretion, and restoring gut microbiota homeostasis, providing a scientific basis for developing probiotic-based functional foods against HUA.

Helicobacter pylori (Hp), a Class I carcinogen infecting over 50% of the global population, is increasingly resistant to conventional antibiotics. This study presents an AI-engineered probiotic strategy targeting urease, a key Hp virulence factor. A humanized single-domain antibody (UreBAb), previously identified and selected in our laboratory, was synthesized commercially and modeled using AlphaFold2, with structural validation conducted via SAVES 6.0. Molecular docking (PyMOL/ClusPro2) and binding energy analysis (InterProSurf) identified critical urease-active residues: K40, P41, K43, E82, F84, T86, K104, I107, K108, and R109. Machine learning-guided optimization using mCSA-AB, I-Mutant, and FoldX prioritized four mutational hotspots (K43, E82, I107, R109), leading to the generation of nine antibody variants. Among them, the I107W mutant exhibited the highest activity, achieving 65.6% urease inhibition—a 24.95% improvement over the wild-type antibody (p < 0.001). Engineered Escherichia coli Nissle 1917 (EcN) expressing the I107W antibody significantly reduced gastric HP colonization by 4.42 log10 CFU in the treatment group and 3.30 log10 CFU in the prevention group (p < 0.001 and p < 0.05, respectively), while also suppressing pro-inflammatory cytokine levels. Histopathological (H&E) analysis confirmed that the I107W antibody group showed significantly enhanced mucosal repair compared to wild-type probiotic-treated mice. Notably, 16S rRNA sequencing revealed that intestinal microbiota diversity and the abundance of core microbial species remained stable across different ethnic backgrounds. By integrating AI-guided antibody engineering with targeted probiotic delivery, this platform provides a transformative and microbiota-friendly strategy to combat antibiotic-resistant Hp infections.