Boterzuur-vormende darmbacterien: een nieuwe behandeling tegen niet alcoholische leververvetting
Every year, more patients develop non-alcoholic fatty liver disease, or MASLD. This increasing liver problem is strongly related to (extreme) overweight and type 2 diabetes. The excess of liver fat can turn into liver inflammation, followed by fibrosis and scarring, and ultimately by cirrhosis and liver failure. In addition, many patients suffer from cardiovascular disease, because MASLD promotes high cholesterol and inflammation, two processes that greatly contribute to atherosclerosis. The problem of MASLD is still insufficiently recognized by doctors and patients in the Netherlands. There is also no registered drug treatment available yet. On the other hand, given the extent and severity of the problem, there is a clear need for treatment, all the more so because lifestyle management alone cannot stop the disease process in severe forms of MASLD
A new insight is that intestinal bacteria influence the MASLD disease process. Certain gut bacteria convert nutrients into substances that can inhibit liver inflammation in the MASLD disease process. We showed that patients with a severe form of MASLD liver inflammation have fewer potential protective gut bacteria. The most important potentially protective intestinal bacterium is Eubacterium hallii, probably due to the production of the substance butyric acid. In an overweight mouse model, treatment with E. hallii produced less liver fat and fat production in the liver. Encouraged by these positive findings, we - the Amsterdam UMC (location AMC and VUmc), in partnership with Wageningen University and Caelus Pharmaceuticals - want to develop E. hallii as probiotic treatment for MASLD. In this proposal we want to take a crucial developmental step of this new treatment: testing E. hallii in mouse models that are specific for MASLD (not just overweight). We also investigate the protective effects of E. hallii and of butyric acid, aided by a MASLD liver cell model. If the findings are positive, this paves the way for an innovative treatment of patients with MASLD: the E. hallii probiotic.
Indeed we were able to establish a MASLD mouse model and test E. hallii, now termed A. soehngenii, in it. It did not reduce MASLD, yet early changes including effect on gluconeogenesis in the gut and reduction of lipogenesis genes in liver were observed. This led to a new research program including a trial in patients with MASLD combining A. soehngenii with two other probiotics and capsules with gut bacteria of vegan donors to test the potential of the gut microbiome to reduce MASLD via the gut-liver axis.
