Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations

Yueqiong Ni¹, Lingling Qian², Sara Leal Siliceo³, Xiaoxue Long², Emmanouil Nychas³, Yan Liu⁴, Marsena Jasiel Ismaiah⁵, Howell Leung³, Lei Zhang², Qiongmei Gao², Qian Wu², Ying Zhang², Xi Jia⁴, Shuangbo Liu⁶, Rui Yuan⁶, Lina Zhou⁷, Xiaolin Wang⁷, Qi Li⁷, Yueliang Zhao⁶, Hani El-Nezami⁵, Aimin Xu⁸, Guowang Xu⁹, Huating Li¹⁰, Gianni Panagiotou¹¹, Weiping Jia¹²

Affiliations

¹ 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.
² 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.
³ Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany.
⁴ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, China.
⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio 70211, Finland; School of Biological Sciences, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.
⁶ College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
⁷ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
⁸ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.
⁹ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: xugw@dicp.ac.cn.
¹⁰ 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. Electronic address: huarting99@sjtu.edu.cn.
¹¹ Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany; Department of Medicine, The University of Hong Kong, Hong Kong, China; Friedrich Schiller University, Faculty of Biological Sciences, Jena, Germany. Electronic address: gianni.panagiotou@leibniz-hki.de.
¹² 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. Electronic address: wpjia@sjtu.edu.cn.

PMID: 37673036
DOI: 10.1016/j.cmet.2023.08.002

Free article

Randomized Controlled Trial

Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations

Yueqiong Ni et al. Cell Metab. 2023.

Free article

. 2023 Sep 5;35(9):1530-1547.e8.

doi: 10.1016/j.cmet.2023.08.002.

Authors

Affiliations

¹ 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.
² 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.
³ Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany.
⁴ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, China.
⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio 70211, Finland; School of Biological Sciences, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.
⁶ College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
⁷ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
⁸ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.
⁹ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: xugw@dicp.ac.cn.
¹⁰ 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. Electronic address: huarting99@sjtu.edu.cn.
¹¹ Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany; Department of Medicine, The University of Hong Kong, Hong Kong, China; Friedrich Schiller University, Faculty of Biological Sciences, Jena, Germany. Electronic address: gianni.panagiotou@leibniz-hki.de.
¹² 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. Electronic address: wpjia@sjtu.edu.cn.

PMID: 37673036
DOI: 10.1016/j.cmet.2023.08.002

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.

Keywords: BCAAs; Bacteroides stercoris; gut microbiota; intrahepatic triglyceride content; lipopolysaccharides; microbiota transplantation; microbiota-directed foods; non-alcoholic fatty liver disease; resistant starch.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Comment in

Vive la resistant starch: A potential treatment for metabolic dysfunction-associated steatohepatitis.
Zhang X, Yu J, Wong VW. Zhang X, et al. Cell Metab. 2023 Sep 5;35(9):1491-1493. doi: 10.1016/j.cmet.2023.07.004. Cell Metab. 2023. PMID: 37673032

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Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations

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Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Publication types

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LinkOut - more resources

Full Text Sources

Medical