Hepatobiliary and pancreatic: Multi‐donor fecal microbiota transplantation attenuated high‐fat diet‐induced hepatic steatosis in mice by remodeling the gut microbiota

Abstract Background and Aims Fecal 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. Methods Fecal 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. Results Fecal 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 . Conclusion NAFLD 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.