Exploring the pathogenesis of NAFLD: a study of the correlation of gut microbes and metabolites in humanized mouse gut microbiota.

Abstract

There is mounting scientific evidence indicating a robust association between gut microbiota and nonalcoholic fatty liver disease (NAFLD). Exposure to commensal microbiota in germ-free mice has a significant impact on the regulatory mechanisms of gut genes, in contrast to those conventionally raised. In this study, we have successfully inoculated the gut microbiota from healthy individuals and NAFLD patients into germ-free mice, with the objective of developing a humanized mouse model that accurately replicates the gut microenvironment of NAFLD patients. Changes in blood composition and liver pathology in these mice were systematically measured. Furthermore, we have conducted a detailed analysis of the variations in fecal microbiota and differential metabolites in the blood composition. Our findings indicate a high degree of similarity in disease characteristics between mice colonized with microbiota and humans suffering from NAFLD. Notably, we have observed a strong correlation between alterations in serum differential metabolites and gut microbiota in these mice. KEY MESSAGES: A humanized NFALD mouse model was established based on sterile mice. In microbiota-colonized mice and humans with NAFLD, disease characteristics showed a high degree of similarity. There was a strong association between changes in serum differential metabolites and gut microbiota in mice colonized by intestinal microbiota.