摘要：SummaryNon-alcoholic fatty liver disease (NAFLD) is now the most frequent global chronic liver disease. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by extrahepatic cancers and liver and cardiovascular disease. Once the disease is established, women have a higher risk of disease progression and worse outcome. It is therefore critical to deepen the current knowledge on the pathophysiology of NAFLD in women. Here, we used a systems biology approach to investigate the contribution of different organs to this disease. We analyzed transcriptomics profiles of liver and adipose tissues, fecal metagenomes, and plasma metabolomes of 55 women with and without NAFLD. We observed differences in metabolites, expression of human genes, and gut microbial features between the groups and revealed that there is substantial crosstalk between these different omics sets. Multi-omics analysis of individuals with NAFLD may provide novel strategies to study the pathophysiology of NAFLD in humans.Graphical abstractDisplay OmittedHighlights•The gut microbiome is significantly different between women with and without NAFLD•The NAFLD plasma metabolome is characterized by lipid and amino acids post prandial•Women with NAFLD have distinct transcriptional profiles in liver and adipose tissue•Women with NAFL have a different response upon MMT after massive weight lossBiological sciences; Physiology; Human metabolism; Systems biology
