A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease

Runtan Cheng, Lu Wang, Shenglong Le, Yifan Yang, Can Zhao, Xiangqi Zhang, Xin Yang, Ting Xu, Leiting Xu, Petri Wiklund, Jun Ge, Dajiang Lu, Chenhong Zhang (), Luonan Chen () and Sulin Cheng ()
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Runtan Cheng: Shanghai Jiao Tong University
Lu Wang: Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences
Shenglong Le: Shanghai Jiao Tong University
Yifan Yang: Shanghai Jiao Tong University
Can Zhao: Shanghai University of Sport
Xiangqi Zhang: Shanghai Jiao Tong University
Xin Yang: Shanghai Jiao Tong University
Ting Xu: Shanghai Jiao Tong University
Leiting Xu: Shanghai Jiao Tong University
Petri Wiklund: Shanghai Jiao Tong University
Jun Ge: Shanghai Jiao Tong University
Dajiang Lu: Shanghai Jiao Tong University
Chenhong Zhang: Shanghai Jiao Tong University
Luonan Chen: Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences
Sulin Cheng: Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Exercise and diet are treatments for nonalcoholic fatty liver disease (NAFLD) and prediabetes, however, how exercise and diet interventions impact gut microbiota in patients is incompletely understood. We previously reported a 8.6-month, four-arm (Aerobic exercise, n = 29; Diet, n = 28; Aerobic exercise + Diet, n = 29; No intervention, n = 29) randomized, singe blinded (for researchers), and controlled intervention in patients with NAFLD and prediabetes to assess the effect of interventions on the primary outcomes of liver fat content and glucose metabolism. Here we report the third primary outcome of the trial—gut microbiota composition—in participants who completed the trial (22 in Aerobic exercise, 22 in Diet, 23 in Aerobic exercise + Diet, 18 in No Intervention). We show that combined aerobic exercise and diet intervention are associated with diversified and stabilized keystone taxa, while exercise and diet interventions alone increase network connectivity and robustness between taxa. No adverse effects were observed with the interventions. In addition, in exploratory ad-hoc analyses we find that not all subjects responded to the intervention in a similar manner, when using differentially altered gut microbe amplicon sequence variants abundance to classify the responders and low/non-responders. A personalized gut microbial network at baseline could predict the individual responses in liver fat to exercise intervention. Our findings suggest an avenue for developing personalized intervention strategies for treatment of NAFLD based on host-gut microbiome ecosystem interactions, however, future studies with large sample size are needed to validate these discoveries. The Trial Registration Number is ISRCTN 42622771.

Date: 2022
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DOI: 10.1038/s41467-022-29968-0

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