Affiliation:
1. Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine South China University of Technology Guangzhou China
2. Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center Guangzhou First People's Hospital Guangzhou China
Abstract
AbstractBackground and AimsFecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single‐donor (SD) or multi‐donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms.MethodsFecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal‐chow diet (NCD) or a high‐fat diet (HFD) for 3 weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12 weeks.ResultsFecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD‐FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD‐fed mice. Compared to untreated HFD‐fed mice, MD‐FMT significantly decreased the relative expression of IL‐1β, IL‐6, TNF‐α, IFN‐γ, and IL‐1β mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin‐1, occludin, and E‐cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD‐FMT intervention. Furthermore, FMT reversed HFD‐induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia.ConclusionNAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD‐fed controls. MD‐FMT restored gut dysbiosis in HFD‐fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.
Funder
National Natural Science Foundation of China
Science and Technology Planning Project of Guangdong Province
Natural Science Foundation of Guangdong Province
Guangzhou Municipal Science and Technology Project
Subject
Gastroenterology,Hepatology