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

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.

Gut microbiota and related metabolites in the pathogenesis of nonalcoholic steatohepatitis and its resolution after bariatric surgery

“…109,110 Also, in a recent study, Gao et al evaluated the role of the gut microbiota in the improvement of NAFLD after duodenaljejunal bypass surgery, finding that the improvement in hepatic steatosis in operated rats was associated with substantial changes in the microbiota. 111 Moreover, it has been reported that SG leads to an increase in gene richness and bacterial diversity of the gut microbiota in individuals with obesity, indicating that the microbiome in these patients becomes more similar to the microbiome in lean control following SG and weight loss. 94 Hence, some of the deleterious consequences affecting NAFLD originated from obesity-related gut microbiota dysbiosis could be reversed by BS.…”