One of the leading causes of chronic liver damage in the US is alcohol abuse. New research into the disease's etiology shows a surprising role for gut bacteria in the ruination of the liver.
Around half of end-stage liver disease cases, also known as liver cirrhosis, are caused by alcohol.
Overall, liver cirrhosis is the 10th biggest killer in the US.
Science already has an understanding of how alcohol can directly impact the liver's health; the metabolic products of the breakdown of alcohol are toxic to the liver.
Additionally, the inflammation that these secondary compounds produce can be harmful to the organ's functioning.
New research published this week in Cell Host & Microbe shows how a secondary mechanism, involving bacteria in the gut, also plays a significant role in the liver's downfall.
Dr. Bernd Schnabl and his team at the University of California found that alcohol can suppress antibacterial defense systems within the intestines, causing further damage to the liver.
Mouse guts, lectins and bacteria
REG3B and REG3G lectins are produced by specific cells of the intestinal wall and act as natural antibiotics. Chronic alcohol intake has been found to hinder the production of these proteins.
Reduction in REG3B and REG3G allows bacteria to replicate freely; they are also able to move through the intestinal wall with greater ease. Once on the other side of the intestinal wall, the bacteria can hitch a ride in the blood vessels surrounding the gut.
All blood passes through the liver; this ensures that nutrients can be processed and toxins broken down. It also allows the newly freed bacteria to make their way to the liver and enhance the damage being wrought by the alcohol.
To test the negative impact of this mechanism, Dr. Schnabl and his team engineered REG3G-deficient mice. These mice showed an excess of bacteria in their guts and a matching increase in liver damage caused by alcohol use.
Conversely, when REG3G was over-expressed in the intestine, the mice showed lower levels of bacteria and a reduction in liver disease, compared with their brothers and sisters.
To check the relevance of the findings in humans, levels of gut bacteria were measured in humans with alcohol dependency. As expected, quantities of bacteria were found to be significantly elevated.
It seems clear that these lectins play a role in the liver damage caused by alcohol. Medical News Today asked Dr. Schnabl how significant this bacterial role might be in the overall disease; he considers it to be "a substantial contribution."
The future of liver cirrhosis research
This fresh information opens new avenues for those investigating ways to minimize the damage caused by alcohol. MNT asked Dr. Schnabl whether there might be other molecules that are negatively impacted by alcohol consumption. Although his previous research had not found the suppression of any other natural antimicrobials, he said:
"It is certainly conceivable that other 'endogenous antibiotics' produced by the intestine also help keep the mucosa clean from colonizing bacteria."
Of course, the most effective way to reduce alcohol damage to the liver is to stop drinking alcohol. For a number of reasons, this cannot always be achieved. In the future, drugs that enhance the intestine's production of REG3G could help the liver fend off some of the imminent damage.
When MNT asked Dr. Schnabl about any future investigations in a similar vein, he said:
"Future research will have two directions: can we identify other molecules or strategies to increase REG3 expression which could be used as a therapeutic approach in patients with alcoholic liver disease.
It will also be important to determine whether there are certain bacteria in the mucosa-associated microbiota that exacerbate liver disease."
Despite alcohol having walked hand in hand with human culture for millennia, we still have a lot to learn about the damage it can cause. MNT recently covered research showing that binge drinking plus chronic alcohol use damages the liver more than expected.