The human body plays host to trillions of microorganisms. There is growing realization that the human body is a “super” ecosystem where the host, i.e. the body, lives in harmony with these large number of microbes. Not only does the body live in harmony, but also there is a symbiotic relationship between the microbes and the body which is essential for good health. The biggest populations of microbes live in the gut. Bacteria in the gut are essential in digestion as they help us break down complex molecules in meat and vegetables. The gut microbiota present at birth allow for adaptive immunity. This means that our immune system learns how to respond to bacteria through this initial interaction with gut organisms. Many diseases have been linked to changes in gut microbiota and liver disease is no exception.
The liver is the organ with the closest proximity to the gut and therefore is exposed to large numbers of bacteria. Conditions such as alcoholic and non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. The altered gut microbiome in these conditions may influence the degree of fat, inflammation and fibrosis that develop in the liver. Although not well studied, changes in the colon microbiome have been associated with the development of cirrhosis and one of its complications, hepatic encephalopathy or confusion. Hepatic encephalopathy can be successfully treated with medications such as probiotics or antibiotics that have the ability to change the composition of the gut bacteria to one that is more favorable for less disease.
Gut microbiome is a major factor in maintaining the integrity of the intestinal mucosa and therefore regulating absorption into the bloodstream. When the gut microbiome is altered, bacteria can enter the bloodstream and make their way to the liver. In the liver, inflammatory components are then stimulated and these may result in liver inflammation and fibrosis. Additionally, the bacteria in the blood can result in sepsis as well as peritonitis, especially in people with liver disease.
The best-studied effects of gut bacteria are in the development and treatment of non-alcoholic fatty liver disease. Gut bacteria have been shown to be able to react with specific liver receptors and increase inflammatory markers leading to liver inflammation, insulin resistance and diabetes. Treatment with probiotics has been shown to decrease fat in the liver as well as decrease serum triglycerides and VLDL levels.
We are still learning about the effects of altered gut bacteria and systemic disease, including liver disease. It makes sense that altering the natural relationship between humans and bacteria can lead to disease. There is a growing body of evidence implicating the microbiome in the development of liver disease. More studies are needed in different clinical situations to manipulate the microbiota by various strategies including prebiotics, new probiotics and/or antibiotics. We need to establish in the future how manipulation of the gut microbiota might prove beneficial for the treatment of patients with various liver diseases at either early or later disease stages. This should prove to be very exciting and rewarding and hopefully will attract physicians to investigate all these possibilities.
David Bernstein, MD, FAASLD,FACG, AGAF, FACP, is the chief of hepatology at Sandra Atlas Bass Center for Liver Diseases and a professor of medicine at Hofstra-Northwell School of Medicine.