The trillions of microorganisms that comprise the human gut microbiota play many important roles in human health. These organisms can aid in the development of the immune system prevent the onset of autoimmune disease, and help with nutrient metabolism. In Monday’s Hans Popper State-of-the-Art Lecture “Gut Microbiota and Liver” Bernd Schnabl, MD, Associate Professor of Gastroenterology at the University of California San Diego School of Medicine, will discuss the role of the gut microbiota in liver disease.
“The gut microbiota can either contribute to or protect from liver disease depending on the disease context,” said Dr. Schnabl.
Many patients with chronic liver disease and, in particular, cirrhotic patients have intestinal bacterial overgrowth. In addition, the composition of the bacterial microbiome and fungal mycobiome changes during the onset and progression of disease. For example, patients with nonalcoholic fatty liver disease have different microbiota than those patients with chronic liver disease due to alcohol abuse. The same is true for patients with end-stage liver disease compared with those with pre-cirrhotic liver disease.
Modulation of liver disease-associated dysbiosis is an attractive target for therapy for these diseases.
“We can use ‘untargeted’ approaches, such as using probiotics or antibiotics that can affect the overall structure of microbiota,” Dr. Schnabl said. “But we also have targeted and precision-medicine approaches available such as transplantation of more precise microbial communities, engineered bacterial strains or drugs that target specific bacterial enzymes and metabolites.”
During his lecture, Dr. Schnabl plans to cover a number of topics related to the gut microbiota, including how gut dysbiosis induces intestinal inflammation and causes progression of organ damage.
“We know now that in many pre-cirrhotic conditions the onset of dysbiosis can cause a subclinical intestinal inflammation,” Dr. Schnabl said. “These inflammatory changes trigger onset of gut barrier dysfunction, or what we call leaky gut.”
According to Dr. Schnabl, increased intestinal permeability allows microbial products to translocate from the intestine to the portal vein circulation. The portal vein drains all blood from the intestine to the liver.
“The liver is the first organ that encounters not only nutrients from the intestines but toxins or microbial products as well,” Dr. Schnabl said. “If there is a gut barrier dysfunction in the intestines triggered by changes in gut microbiota, chronic exposure of the liver to microbial metabolites and products will exacerbate hepatic disease.”
Dr. Schnabl will discuss how many liver diseases are driven by intestinal dysbiosis and how these diseases can be affected with modulation of dysbiosis.
“We are not there yet. We need to better understand host-microbial interactions, which will allow us to discover novel therapeutic targets in the gut microbiota,” Dr. Schnabl said. “This will help in developing new therapeutic strategies for our patients with liver disease.”