Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, Hohhot, Inner Mongolia, China.
Pharmacol Res. 2024 Nov;209:107445. doi: 10.1016/j.phrs.2024.107445. Epub 2024 Oct 11.
Gout is characterized by dysregulation of uric acid (UA) metabolism, and the gut microbiota may serve as a regulatory target. This two-month randomized, double-blind, placebo-controlled trial aimed to investigate the additional benefits of coadministering Probio-X alongside febuxostat. A total of 160 patients with gout were randomly assigned to either the probiotic group (n = 120; Probio-X [3 × 10 CFU/day] with febuxostat) or the placebo group (n = 40; placebo material with febuxostat). Coadministration of Probio-X significantly decreased serum UA levels and the rate of acute gout attacks (P < 0.05). Based on achieving a target sUA level (360 μmol/L) after the intervention, the probiotic group was further subdivided into probiotic-responsive (ProA; n = 54) and probiotic-unresponsive (ProB; n = 66) subgroups. Post-intervention clinical indicators, metagenomic, and metabolomic changes in the ProB and placebo groups were similar, but differed from those in the ProA group, which exhibited significantly lower levels of acute gout attack, gout impact score, serum indicators (UA, XOD, hypoxanthine, and IL-1β), and fecal gene abundances of UA-producing pathways (KEGG orthologs of K13479 and K01487; gut metabolic modules for formate conversion and lactose and galactose degradation). Additionally, the ProA group showed significantly higher levels (P < 0.05) of gut SCFAs-producing bacteria and UA-related metabolites (xanthine, hypoxanthine, bile acids) after the intervention. Finally, we established a gout metagenomic classifier to predict probiotic responsiveness based on subjects' baseline gut microbiota composition. Our results indicate that probiotic-driven therapeutic responses are highly individual, with the probiotic-responsive cohort benefitting significantly from probiotic coadministration.
痛风的特征是尿酸（UA）代谢失调，肠道微生物群可能是一个调节靶点。这项为期两个月的随机、双盲、安慰剂对照试验旨在研究联合使用 Probio-X 与非布司他的额外益处。共有 160 名痛风患者被随机分为益生菌组（n = 120；Probio-X [3 × 10 CFU/天]与非布司他）或安慰剂组（n = 40；安慰剂材料与非布司他）。联合使用 Probio-X 可显著降低血清 UA 水平和急性痛风发作率（P < 0.05）。基于干预后达到目标 sUA 水平（360 μmol/L），益生菌组进一步细分为益生菌反应（ProA；n = 54）和益生菌无反应（ProB；n = 66）亚组。干预后，ProB 组和安慰剂组的临床指标、宏基因组和代谢组学变化相似，但与 ProA 组不同，ProA 组的急性痛风发作、痛风影响评分、血清指标（UA、XOD、次黄嘌呤和 IL-1β）和产生 UA 的途径的粪便基因丰度（KEGG 直系同源物 K13479 和 K01487；甲酸转化和乳糖及半乳糖降解的肠道代谢模块）显著较低。此外，ProA 组在干预后具有更高水平（P < 0.05）的产生 SCFAs 的肠道细菌和与 UA 相关的代谢物（黄嘌呤、次黄嘌呤、胆汁酸）。最后，我们建立了一个痛风宏基因组分类器，根据受试者的基线肠道微生物群组成来预测益生菌的反应性。我们的结果表明，益生菌驱动的治疗反应具有高度的个体差异，益生菌反应性队列从益生菌联合治疗中显著获益。
