Fecal Microbiota Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiota in Non-Alcoholic Fatty Liver Disease (NAFLD)

Abstract

Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

“…Following these premises, translational studies were conducted, with particular regard to NAFLD disease. In one study the intestinal microbiota collected from obese donors before and after weight loss was transplanted into GF mice: Mice that received intestinal microbiota before weight loss had higher triglycerides and cholesterol liver levels than mice that received intestinal microbiota after weight loss [180]. Moreover, donor fecal microbiota transplantation studies performed in human subjects confirmed that the gut dysbiosis can per se cause hepatic steatosis mainly by means of weight gain, insulin resistance, and increased OS [67,181,182].…”

Aldehyde Dehydrogenase Mutation Exacerbated High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease with Gut Microbiota Remodeling in Male Mice

“…Human and animal studies demonstrated a potential causal role of the gut microbiota in NAFLD. Mice received human NAFL microbiota and were subsequently fed a high-fructose, high-fat diet, leading them to gain more weight and have a higher number of liver triglycerides than that of mice that received healthy human microbiota [ 11 ]. The abundance of Ruminococcaceae and Tannerellaceae was increased, and the abundance of Desulfovibrionaceae and Rikenellaceae was decreased in the mice receiving human NAFL microbiota [ 11 ].…”

“…Mice received human NAFL microbiota and were subsequently fed a high-fructose, high-fat diet, leading them to gain more weight and have a higher number of liver triglycerides than that of mice that received healthy human microbiota [ 11 ]. The abundance of Ruminococcaceae and Tannerellaceae was increased, and the abundance of Desulfovibrionaceae and Rikenellaceae was decreased in the mice receiving human NAFL microbiota [ 11 ]. Fei and colleagues reported that liver inflammation was dependent upon endotoxin expression in HFD-fed NAFLD mice [ 12 ].…”

“…Fei and colleagues reported that liver inflammation was dependent upon endotoxin expression in HFD-fed NAFLD mice [ 12 ]. Animal studies demonstrated a potential causal role of gut microbiota in NAFLD [ 11 , 13 ]. Proteobacteria are enriched in NAFLD and NASH [ 14 ].…”

Beneficial effect of whole-grain wheat on liver fat: a role for the gut microbiota?

“…The dysbiosis also impacts energy harvest from the diet and alters the hepatic expression of genes involved in de novo lipogenesis. Altogether, these microbiota-associated mechanisms may influence steatosis development and fecal microbiota transplants recently confirmed that the gut bacteria affect hepatic lipid accretion (8).…”