Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany; Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany.
Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Cell Metab. 2023 Sep 5;35(9):1530-1547.e8. doi: 10.1016/j.cmet.2023.08.002.
Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. To investigate the effects of resistant starch (RS) as a microbiota-directed dietary supplement for NAFLD treatment, we coupled a 4-month randomized placebo-controlled clinical trial in individuals with NAFLD (ChiCTR-IOR-15007519) with metagenomics and metabolomics analysis. Relative to the control (n = 97), the RS intervention (n = 99) resulted in a 9.08% absolute reduction of intrahepatic triglyceride content (IHTC), which was 5.89% after adjusting for weight loss. Serum branched-chain amino acids (BCAAs) and gut microbial species, in particular Bacteroides stercoris, significantly correlated with IHTC and liver enzymes and were reduced by RS. Multi-omics integrative analyses revealed the interplay among gut microbiota changes, BCAA availability, and hepatic steatosis, with causality supported by fecal microbiota transplantation and monocolonization in mice. Thus, RS dietary supplementation might be a strategy for managing NAFLD by altering gut microbiota composition and functionality.
非酒精性脂肪性肝病 (NAFLD) 是一种代谢功能障碍的肝脏表现，目前缺乏有效的干预措施。为了研究抗性淀粉 (RS) 作为一种针对肠道菌群的饮食补充剂对 NAFLD 治疗的影响，我们将一项为期 4 个月的、针对 NAFLD 患者的随机安慰剂对照临床试验（ChiCTR-IOR-15007519）与宏基因组学和代谢组学分析相结合。与对照组（n=97）相比，RS 干预组（n=99）的肝内甘油三酯含量（IHTC）绝对减少了 9.08%，而调整体重减轻后则减少了 5.89%。血清支链氨基酸 (BCAA) 和肠道微生物种类，特别是粪拟杆菌，与 IHTC 和肝酶显著相关，且 RS 可降低其水平。多组学综合分析揭示了肠道菌群变化、BCAA 可用性和肝脂肪变性之间的相互作用，粪便微生物移植和单定植实验在小鼠中支持了因果关系。因此，RS 饮食补充可能是通过改变肠道菌群组成和功能来治疗 NAFLD 的一种策略。
