Baseline gut microbiome as a predictive biomarker of response to probiotic adjuvant treatment in gout management

• Published in: Pharmacological research Vol. 209; p. 107445
• Main Authors: Zhao, Feiyan, Tie, Ning, Kwok, Lai-Yu, Ma, Teng, Wang, Jing, Man, Dafu, Yuan, Xiangzheng, Li, Huiyun, Pang, Lixia, Shi, Hui, Ren, Shuiming, Yu, Zhongjie, Shen, Xin, Li, Hongbin, Zhang, Heping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2024
• Subjects: Adult; Aged; Biomarkers - blood; Double-Blind Method; Febuxostat; Febuxostat - therapeutic use; Feces - microbiology; Female; Gastrointestinal Microbiome - drug effects; Gout - blood; Gout - drug therapy; Gout Suppressants - therapeutic use; Gut microbiome; Humans; Male; Metabolomics; Middle Aged; Probiotics - administration & dosage; Probiotics - therapeutic use; Short-chain fatty acid; Treatment Outcome; Uric acid; Uric Acid - blood; Metabolomics; Short-chain fatty acid; Uric acid; Febuxostat; Gut microbiome
• ISSN: 1043-6618; 1096-1186; 1096-1186
• DOI: 10.1016/j.phrs.2024.107445

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 × 1010 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. [Display omitted]