Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women

Lesley Hoyles, José-Manuel Fernández-Real, Massimo Federici, Matteo Serino, James Abbott, Julie Charpentier, Christophe Heymes, Jèssica Latorre Luque, Elodie Anthony, Richard H. Barton, Julien Chilloux, Antonis Myridakis, Laura Martinez-Gili, José Maria Moreno-Navarrete, Fadila Benhamed, Vincent Azalbert, Vincent Blasco-Baque, Josep Puig, Gemma Xifra, Wifredo Ricart, Christopher Tomlinson, Mark Woodbridge, Marina Cardellini, Francesca Davato, Iris Cardolini, Ottavia Porzio, Paolo Gentileschi, Frédéric Lopez, Fabienne Foufelle, Sarah A. Butcher, Elaine Holmes, Jeremy K. Nicholson, Catherine Postic, Rémy Burcelin, Marc-Emmanuel Dumas
  • news nature com, June 2018, Springer Science + Business Media
  • DOI: 10.1038/s41591-018-0061-3

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.

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

Lesley Hoyles (Author)
Imperial College London

Changes in levels of microbiome-associated metabolites in our blood are likely to be important to the development and/or progression of a range of diseases. In the future, diagnostic tests for diseases may be based on levels of these metabolites in our blood rather than more invasive methods such as liver biopsy or expensive scanning methods.

The following have contributed to this page: Lesley Hoyles