16 Feb 2016 New clues to what really causes alcoholic liver cirrhosis
Livers and alcohol do not get on well together. That is well known. But precisely how alcohol destroys the liver of someone who drinks too much has been a mystery. New research is pointing to the role of gut bacteria, reports The Economist.
Though alcohol (technically, ethanol—the type of alcohol that has two carbon atoms and is produced by yeast fermentation) wreaks some damage directly, experiments suggest this is by no means the whole explanation. The serious and irreversible harm of cirrhosis seems to have another cause, hitherto unknown. Now, though, perhaps it has been unmasked.
A team of medical researchers led by Bernd Schnabl of the University of California, San Diego, suggest the culprit is alcohol’s effect on the gut, and the bacteria therein.
Fortunately for those who like a pint or a dram, the liver is a regenerative marvel. New cells constantly take the places of old ones. Indeed, huge chunks can be cut from the organ, only to grow back within days. This is just as well, for one of the liver’s tasks is to deal with the stream of toxic chemicals people ingest as part of their food and drink. Ethanol is one of these.
Though large quantities may induce a build-up of hepatic fat known as steatosis, abstinence will often reverse this. But even the liver can stand only so much. The scarring involved in cirrhosis is a one-way trip that ends in the organ’s failure.
Curious effect of antibiotics
One curiosity is that certain antibiotics seem to ameliorate alcohol’s effect on the liver. The livers of mice given antibiotics which clear their intestines of bacteria before they are dosed with ethanol suffer far less damage than those of similar animals not so dosed.
Five years ago that knowledge prompted Dr Schnabl to start looking into the relationship between alcohol and gut bacteria. His latest findings have just been published in Cell Host and Microbe.
Over the course of his research Dr Schnabl found that heavy consumption of alcohol hampers the intestine’s antibacterial defence system. In particular, it suppresses production of two proteins called REG3B lectin and REG3G lectin. These keep the number of bacteria in the gut under control, so their sudden absence leads to a population explosion. And that, Dr Schnabl hypothesised, lets bacteria escape through the intestinal wall to the liver.
To test this idea he designed an experiment. For eight weeks, he and his colleagues fed ethanol both to ordinary mice and to mice genetically engineered to lack the two pertinent lectin molecules. They also engineered some of the rodents’ gut bugs to make the bacteria in question fluoresce. This let them track these bugs, and see if any left the intestines.
They did. As the mice were exposed to more and more alcohol, the glow-in-the-dark bacteria underwent population explosions that let them escape the intestines. Once out, they migrated to the liver, where they triggered strong immune reactions. These drew large numbers of white blood cells into the liver, causing inflammation. The white cells themselves engulf and consume bacteria, but prolonged inflammation also damages host tissue.
Both groups of mice were affected, but the effect was more intense in the lectin-deficient animals. In both their livers and their intestines, their bacterial populations were 50% larger than those of the control mice. As a consequence, they ended up with livers that were much more badly damaged.
The researchers then tried things in reverse. They ran the experiment with mice engineered to produce more lectins than normal, and found these animals could endure extensive exposure to alcohol without developing large bacterial populations or showing any signs of liver damage.
All this suggests that tinkering with the gut bacteria of alcoholic people might help.
Dr Schnabl has started to look into the matter by studying the bacterial populations of eight alcoholics and comparing them with those of five non-alcoholics. Preliminary results indicate that the findings from mice apply to human beings, too. Finding a way to boost REG3-lectin production in those who drink too much might thus do them a power of good.
Source: The Economist
Wang, Lirui et al, Cell Host & Microbe , Volume 19 , Issue 2 , 227 – 239