Abstract：
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.
摘要：
非酒精性脂肪性肝病（NAFLD）是代谢功能障碍的肝脏表现，缺乏有效的干预措施。研究抗性淀粉（RS）作为微生物群导向的膳食补充剂治疗NAFLD的效果。我们将一项针对NAFLD患者的4个月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.相对于对照（n=97），RS干预（n=99）导致肝内甘油三酯含量（IHTC）的9.08％绝对减少，在调整体重减轻后为5.89%。血清支链氨基酸（BCAAs）和肠道微生物种类，特别是杆状拟杆菌，与IHTC和肝酶显着相关，并被RS降低。多组学整合分析揭示了肠道微生物群变化之间的相互作用，BCAA可用性,和肝脏脂肪变性，因果关系由粪便微生物群移植和小鼠单菌落化支持。因此，RS膳食补充可能是通过改变肠道微生物群组成和功能来管理NAFLD的策略。
