The microorganisms in the intestines of many overweight people produce alcohol to an increased extent, as Max Nieuwdorp, professor of Internal Medicine at Amsterdam UMC discovered a few years ago. Breaking down that excessive alcohol leads to fatty liver, which in turn increases the risk of serious diseases such as diabetes and cardiovascular disease. Nieuwdorp has now received an ERC Advanced grant of 2.5 million euros for a major study into the underlying causes of excessive alcohol production. Ultimately, he hopes to find a way to prevent excess alcohol produced in the intestines, and thus the related diseases. In 2022, Nieuwdorp and his team published a study in Nature Medicine on alcohol production in the intestines of overweight patients. "Our findings showed that the turnover of sugars in the intestines of these patients releases far too much alcohol, equivalent to almost half a litre of whisky of alcohol. This is because the composition of the microbiome in their small and large intestines is disrupted. It seems that a change in acidity plays a role in this," Nieuwdorp explains.
Liver has to work hard
For patients, large quantities of alcohol in the intestines can have major consequences. "The liver, as with alcohol from liquor, has to work hard to breakdown the alcohol, and that is done by storing it as fat. This causes people to develop a fatty liver disease that can eventually become inflamed and lead to serious conditions such as cirrhosis of the liver and cardiovascular disease," says Nieuwdorp.
Almost 1 in 5 adults in the Netherlands are overweight and more than 80% of them have fatty liver. Nieuwdorp suspects that the high quantities of sugar in our modern diet can lead to increased alcohol production in the intestines. With the European money from the ERC Advanced grant, he will investigate this further, for example by analyzing the medical data and eating patterns of participants in the long-term HELIUS study.
Bacteria in the gut
Nieuwdorp hopes that the discovery of the increased alcohol production due to the disrupted microbiome in the intestines will create a new path in the search for a way to treat fatty liver disease and liver inflammation. For example, he wants to see if it is possible to control alcohol production in the intestines by equipping bacteria in the intestine with properties that allow them to breakdown more alcohol.
But whether and how that actually works is still unknown. That's what we're going to investigate in this FATGAP-project."
Max Nieuwdorp, Professor of Internal Medicine at Amsterdam UMC
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