The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats.

Yi Gao,Jing Yue,Rongqian Wu,Tieyan Wang,Xiaopeng Yan,Zheng Wu,Yifan Ren,Xiao Xiao,Yi Lv,Jia Zhang

doi:10.3389/fcimb.2021.640448

Abstract

Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide and a major risk factor for the development of end-stage liver disease and hepatocellular carcinoma (HCC) (Sanyal, 2019; Benhammou et al, 2020; Lazarus et al, 2020)
We found that duodenal-jejunal bypass surgery (DJB) alleviated hepatic steatosis in high fat diet (HFD)-fed rats, which was associated with substantial compositional changes in the gut microbiota
Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats attenuated hepatic steatosis. These findings accentuate the role of the gut microbiota in HFD-induced nonalcoholic steatohepatitis (NASH) as well as DJB-associated improvement of hepatic steatosis under such a condition

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide and a major risk factor for the development of end-stage liver disease and hepatocellular carcinoma (HCC) (Sanyal, 2019; Benhammou et al, 2020; Lazarus et al, 2020). It ranges in severity from simple steatosis (excessive fat accumulation) to nonalcoholic steatohepatitis (NASH, liver cell injury and inflammation). The underlying basis for such an improvement is still incompletely understood

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