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DOI: 10.1055/s-0036-1584055
The role of prophylactic treatment with A. muciniphila in the acute alcoholic liver disease
Introduction: Alcoholic liver disease (ALD) is a major cause for liver related deaths. ALD includes a clinical spectrum ranging from steatosis over alcoholic steatohepatitis (ASH) to liver fibrosis and hepatocellular carcinoma (HCC). Alcohol induces intestinal bacterial overgrowth and dysbiosis, these conditions are moreover associated with increased levels of lipopolysaccharides (LPS) and an altered gut barrier. Direct toxic impact of ethanol on the hepatocyte and translocation of LPS from the gut into the liver, play an important role in the pathogenesis of ALD. It was shown for A. muciniphila, a commensal bacterium, to restore gut barrier damage and thereby reducing systemic LPS levels.
Material and Methods: Female wildtype mice were treated with 1,5 × 109 CFU of A. muciniphila on two days prior to alcohol administration (6 g ethanol/kg bodyweight). Eight hours after the gavage of ethanol, mice were sacrificed and samples were collected. To measure in-vivo gut permeability, FITC-Dextran was gavaged four hours after alcohol administration, followed by concentration measurements in the serum.
Results: Ethanol administration led to significant higher levels of ALT (p < 0,05), whereas prophylactic treatment with A. muciniphila lead to significant decreased ALT levels (p < 0,01). We further investigated the numbers of A. muciniphila in stool samples. Alcohol administration reduced the number of A. muciniphila significantly (p < 0,001), independently if A. muciniphila was administered or not. Although we could see a reduction of FITC levels in probiotic treated mice, suggesting a restoration of the gut barrier, we couldn't see improved endotoxemia. Furthermore we could see a trend towards a reduced expression of pro-inflammatory cytokines, although just Tnf-alpha levels were significantly reduced by A. muciniphila treatment (p < 0,05).
Conclusion: Our date indicate a potential role of A. muciniphila in the prophylactic treatment for ALD, but further experiments, in particularly for chronic alcohol consumption, should follow.