Article
作者: Zhang, Mingliang ; Fang, Qichen ; Ni, Yueqiong ; Lu, Yuwei ; Chu, Chengshuang ; Liu, Zhenmin ; Zhang, Lei ; Zeng, Rong ; Wei, Li ; Kang, Piao ; Yang, Jingyi ; Chen, Anran ; Sun, Liming ; Zhu, Xuexue ; Li, Qian ; Guo, Jingyi ; Wu, Zhengjun ; Cheng, Di ; Xiao, Yuanyuan ; Panagiotou, Gianni ; Liu, Dan ; Chen, Feng ; Li, Huating ; Long, Xiaoxue ; You, Chunping ; Li, Jun ; Wang, Hui ; Ren, Quanlu ; Gao, Xiaojing ; Jia, Weiping ; Wu, Qingqing ; Zhou, Guiyun ; Zhang, Ruiqi ; Wu, Qian ; Chen, Luonan ; Yang, Ruibao
Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.