A new study has provided a fascinating new insight into how excessive drinking harms the liver, by suggesting that alcohol reduces the body’s ability to regulate gut bacteria populations. Not only does this produce an increase in the number of microbes within the intestine, but it also enables these microorganisms to migrate from the gut to the liver. The study has been published in Cell Host & Microbe.
Antimicrobial proteins within the intestine play a vital role in controlling bacterial populations, ensuring these do not become unbalanced while at the same time destroying pathogens. Among these are a group of compounds called REG3 lectins, which prevent bacteria from accessing the surfaces of the cells that line the intestine, thereby ensuring they do not damage or penetrate the lining of the gut.
Previous studies have demonstrated that chronic alcohol consumption causes a reduction in REG3 lectins, suggesting that drinking may interfere with the biological processes that regulate intestinal bacteria levels. However, exactly how this affects the liver has until now remained poorly understood.
To investigate this, researchers conducted an experiment using mice that had been engineered to lack the antibacterial protein REG3B. These subjects were fed a diet in which ethanol accounted for 36 percent of total calories – sufficient to be classified as chronic alcohol consumption – for eight weeks. At the end of this period, these mice showed more severe symptoms of steatohepatitis – or fatty liver disease – than a separate group of mice which were fed the same diet but did not lack REG3B. This supports the notion that inhibition of certain antimicrobial compounds in the intestine does indeed contribute to the development of liver disorders following excessive alcohol consumption.
The researchers also discovered higher numbers of intestinal bacteria in the livers and mesenteric lymph nodes – small sacks between the intestine and abdominal wall – of these mice. As such, they suggest that the removal REG3B allows these microbes to access the surface of the intestine, before passing through it and entering the lymph nodes, from where they then translocate to the liver.
To back up this presumption, the researchers then conducted the study in reverse, using mice that had been genetically altered to over-produce the protein REG3G. Following eight weeks of ethanol consumption, these mice displayed lower levels of liver injury or inflammation than the controls.
Exactly how bacteria penetrate the intestine is still unknown, as is the mechanism by which they cause steatohepatitis to develop. Consequently, the study authors propose that future research should focus on answering these questions, while also suggesting that the development of new techniques to increase production of REG3 lectins in the intestine may provide an effective means of protection against alcohol-induced liver disease.