The gut microbiome may contribute to susceptibility to developing alcoholic liver disease

Alcoholic liver disease (ALD) is a major public health issue, yet the underlying mechanisms between ethanol consumption and injury to the liver are poorly understood.  Alcoholics vary in their susceptibility to developing ALD and alcoholic hepatitis (AH) despite consuming similar amounts of alcohol.  Taken together, this evidence suggests that other factors contribute to the onset and progression of ALD other than direct toxicity of alcohol.  Intestinal inflammation and pro-inflammatory bacterial products have also been observed in ALD patients and preclinical mice models, and intestinal dysbiosis has been observed in patients with alcohol dependency.  With this in mind, a team of European researchers devised a strategy to demonstrate microbiome dysbiosis as a casual driver of liver injury. 

The researchers transplanted human gut microbiota into germ-free mice, and the mice were then placed on a high-alcohol diet.  Microbiota were harvested from human alcoholic patients with or without AH (or low severity AH).  Mice transplanted with AH-microbiota had marked increases in symptoms of liver disease as compared to those mice that received microbiota transplants from non-AH alcoholic patients.  These include severe liver inflammation (including increases in T lymphocytes and natural killer cells), more necrosis in the liver, and higher intestinal permeability.  Enterobacteria counts were high in sever-AH patients and faecalibacterium genus was associated with AH-microbiota with low severity.  In an interesting spin, the researchers also transferred microbiota from an alcoholic patient without AH to mice with liver lesions.  Interestingly, mice who had received these microbiota displayed a reduction in serum alanine aminotransferase levels and a decrease in liver regeneration, suggesting that these microbiota could even possibly reverse alcohol-induced liver lesions. 

These findings not only support an association between the gut microbiome and susceptibility to developing alcoholic liver disease, but also provide evidence that these bacteria may drive disease onset.  These were important findings that support microbiota-causal effect rather than dysbiosis as a consequence of liver disease.  This data could perhaps promote development of novel diagnostic techniques that assess the gut microbiome or bacterial metabolites of alcoholic patients.  Methods such as manipulating the microbiome as a therapeutic approach for these patients could also be explored. 

The microbiome of alcoholics may contribute to pathologies

We have written before about the microbiome’s association with alcoholism, and how it has been implicated in many of the maladies connected with the disease.  Recently, research out of George Mason University, published in PLoS ONE, explored the molecular mechanisms behind this relationship.   The scientists measured the metabolites that were formed by the microbiome of alcoholics and compared it to healthy controls.  They discovered that the metabolites that differed between the two groups have important implications on gut health.

The scientists measured the volatile molecules that were being effused from the feces of 18 healthy controls and 16 alcoholics.  The alcoholics’ feces contained high levels of an organic compound called tetradecane, which is known to cause oxidative stresses.  Increased oxidative stress in the gut, especially in alcoholics, is associated with increased gut permeability (i.e. leaky gut), and alcoholic steatohepatitis (i.e. a type of liver disease).  Moreover, specific fatty acids, which are known to reduce oxidative stress (antioxidants), were more depleted in alcoholics when compared with healthy controls.  In addition, the alcoholic feces consisted of lower abundances of short chained fatty acids (SCFAs), which are nearly always associated with intestinal health (click the SCFA tag below to learn more).  Finally, other molecules which are associated with health, like caryophyllene and camphene, were decreased in the guts of alcoholics.

Overall these results show the possible mechanisms by which the microbiome contributes to alcoholism.  Specifically, it appears that the alcoholic microbiome may create oxidative stress molecules, which contribute to gut toxicity.  In addition, the scientists suggest this work could be used as an alcoholism diagnostic, as the characteristic metabolites between the groups were statistically significant.