Susceptibility to Alcohol Induced Liver Injury: Driven by Gut Microbiota?

Posted 6th January 2017 by Jane Williams

Over the past decade, the intestinal microbiota has increasingly been recognised as a critical factor in health and disease. My research focuses on the role of the gut microbiome in metabolic diseases and my main aim is to prove causality. Most studies describe the gut microbiota from patients and compare it to healthy controls. In this way, they define dysbiosis, which is an abnormal microbiome associated with a disease. But an association does not tell if the dysbiosis is the cause of the pathology or the consequence of the disease.

Thanks to the existence of germ-free animal models, we can transplant the microbiome from patients to germ-free mice or rats and see whether we can transfer a phenotype or make them more or less susceptible to disease development. For example, by transplanting gut microbiota from alcoholic patients with or without alcoholic liver disease, we have recently demonstrated that the susceptibility to alcohol induced liver injury is driven by the type of gut microbiota present.

The first form of commercialised microbiome takes the form of Faecal Microbiota Transplantation (FMT). This is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. The procedure involves the following steps: oral antibiotic therapy with vancomycin, bowel preparation, and delivery of the faecal suspension. This last step can be performed via retention enema, during colonoscopy, or using a naso-duodenal tube. In the future, I would not be that surprised if the faecal suspension was replaced by a pill containing a healthy microbiome. And this will be probably adapted for other diseases.

Within the next decades, one of the biggest challenges that the microbiome research will have to face is the development of personalised treatments. We cannot really define what a healthy microbiome is. This is probably because a healthy microbiome for someone might not be healthy for someone else. What we have to achieve is to be able to define what should be modified in someone’s microbiome to be healthier to then develop the tools allowing selective changes in the microbiome to reach this goal.

Over the last decade, the importance of the microbiome for host physiology has been revealed as well as its involvement in numerous pathologies. This has led to great promises, in terms of new therapeutics based on the microbiome. Will these promises be fulfilled? The answer to this question will tell us whether the microbiome is overhyped.

Philippe Gérard is Head of the Research Team Food, Gut Microbiota, Metabolic and Brain Disease at the INRA MICALIS Institute. His research has recently established that germfree mice are resistant to diet-induced obesity and insulin resistance and that gut microbiota determines non-alcoholic fatty liver disease.

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Tags: alcohol, liver, microbiome, microbiota