The gut microbiome contributes to fatty liver disease

What is it about?

Fatty liver disease is one of the most common liver diseases in the world, and its prevalence is increasing because of the obesity epidemic. It is a multifactorial disease, but mechanisms contributing to its development and progression are poorly understood. Numerous animal studies have suggested the gut microbiome may contribute to fatty liver disease. We looked at how the gut microbiome contributes to various aspects of fatty liver disease in obese humans, using a combination of metagenomic (gut microbiome), metabolomic (chemicals in blood and urine), transcriptomic (liver gene expression) and clinical data.

Featured Image

Why is it important?

We showed that faecal microbiota transplants from humans with fatty liver disease to mice caused the mice to develop fatty livers. In addition, we showed that a gut-microbiome-produced chemical detectable in blood - phenylacetate - contributes to accumulation of fat in human liver cells and mouse liver. That is, the gut microbiome contributes directly to fatty liver disease. Under normal conditions, insulin signaling regulates glucose, lipid, and energy processes within the body. In metabolic syndrome, insulin signaling is supressed and this can lead to insulin resistance, which left untreated can develop into type 2 diabetes. Fatty liver disease is associated with metabolic syndrome. We showed that insulin resistance is linked with the gene richness of the microbiome in fatty liver disease. That is, fatty liver disease is associated with reduced microbial gene diversity and downregulation of the insulin receptor, a key gene in regulating insulin signaling.

Perspectives