RT Journal Article SR Electronic T1 Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1787 OP 1794 DO 10.1136/gutjnl-2012-303816 VO 62 IS 12 A1 Le Roy, Tiphaine A1 Llopis, Marta A1 Lepage, Patricia A1 Bruneau, Aurélia A1 Rabot, Sylvie A1 Bevilacqua, Claudia A1 Martin, Patrice A1 Philippe, Catherine A1 Walker, Francine A1 Bado, André A1 Perlemuter, Gabriel A1 Cassard-Doulcier, Anne-Marie A1 Gérard, Philippe YR 2013 UL http://gut.bmj.com/content/62/12/1787.abstract AB Objective Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese people and is considered the hepatic manifestation of metabolic syndrome. However, not all obese individuals develop NAFLD. Our objective was to demonstrate the role of the gut microbiota in NAFLD development using transplantation experiments in mice. Design Two donor C57BL/6J mice were selected on the basis of their responses to a high-fat diet (HFD). Although both mice displayed similar body weight gain, one mouse, called the ‘responder’, developed hyperglycaemia and had a high plasma concentration of pro-inflammatory cytokines. The other, called a ‘non-responder’, was normoglycaemic and had a lower level of systemic inflammation. Germ-free mice were colonised with intestinal microbiota from either the responder or the non-responder and then fed the same HFD. Results Mice that received microbiota from different donors developed comparable obesity on the HFD. The responder-receiver (RR) group developed fasting hyperglycaemia and insulinaemia, whereas the non-responder-receiver (NRR) group remained normoglycaemic. In contrast to NRR mice, RR mice developed hepatic macrovesicular steatosis, which was confirmed by a higher liver concentration of triglycerides and increased expression of genes involved in de-novo lipogenesis. Pyrosequencing of the 16S ribosomal RNA genes revealed that RR and NRR mice had distinct gut microbiota including differences at the phylum, genera and species levels. Conclusions Differences in microbiota composition can determine response to a HFD in mice. These results further demonstrate that the gut microbiota contributes to the development of NAFLD independently of obesity.