There is rising trend in the prevalence of fatty liver diseases worldwide; post treatment of hepatitis C virus infection becomes more widespread, fatty liver diseases are probable to become most prevalent liver disorders. Fatty liver diseases are correlated to alcohol, obesity, and the metabolic syndrome, however, their mechanisms of pathogenesis are not yet fully understood. Development and progression of fatty liver, alcoholic, and non-alcoholic liver disease (ALD) all are affected by the composition of the microbiota. Besides, intestinal microbiota have the potential to affect pre-cirrhotic and cirrhotic stages of liver diseases, which open a window of novel strategies for their diagnosis, treatment, and study. 

The current review evaluated the differences and similarities in the cirrhotic and pre-cirrhotic stages of non-alcoholic fatty liver disease (NAFLD) and ALD. Variations are seen in these stages of alcohol-associated disease in patients who continue to drink in contrast to those who stop, in regard to the composition and function of the intestinal microbiota and intestinal integrity. NAFLD and the intestinal microbiota also change between patients with and without diabetes.

Significance of gut microbiota in patients with NAFLD

Patients with NAFLD exhibit lower proportions of Bacteroidetes and higher proportions of Prevotella and Porphyromonas spp in comparison to healthy controls. Disposition to NAFLD is related to increased expression of toll-like receptors (TLRs, TLR4, TLR9), or the tumor necrosis factor (TNF) receptor. The gut microbiota can regulate the severity of NAFLD by increasing synthesis of ethanol, activating TLR signaling and TNF production in the liver, or altering the bile acid profile.

It has been observed that alterations to the intestinal microbiota also affect development of NASH, by affecting digestion, development of obesity, the immune response, and production of gut hormones. Studies evaluating fecal samples from patients with NASH have reduced proportions of Bacteriodetes and increased proportions of Clostridium coccoides. Another study also supported these findings by concluding that Escherichia produce ethanol, and serum concentrations of ethanol are remarkably higher in patients with NASH in contrast to obese or control groups. 

Significance of gut microbiota in patients without cirrhosis

Moreover, studies conducted in chronic alcohol drinkers without cirrhosis or alcoholic hepatitis found that bacterial overgrowth and translocation are essential for disease progression. One trial demonstrated that higher numbers of aerobic and anaerobic bacteria were detected in jejunal aspirates from alcoholic patients than from non-alcoholics. Another study showed that gut leakiness, caused by intestinal barrier dysfunction was seen in patients with alcohol-induced endotoxemia and liver damage. 

Significance of gut microbiota in NAFLD

An altered immune response is often seen in patients with alcoholic hepatitis and cirrhosis and these patients commonly develop infections, correlated with poor outcomes. Alcoholic hepatitis has high mortality, which is partly attributed to systemic inflammatory response syndrome. Several factors play a major role in inflammation in these patients, including alcohol abstinence or level of intake and concurrent use of proton pump inhibitors and/or antibiotics. A study showed that transfer of gut microbiota from a patient with alcoholic hepatitis to germ-free experimental animal revealed increased liver inflammation, in contrast to microbiota from alcoholic patients without any liver injury, which is suggestive of the fact that alcoholic hepatitis-associated microbes play an important role in liver injury. 

Source: Betrapally NS, Gillevet PM, Bajaj JS. Changes in the Intestinal Microbiome and Alcoholic and Nonalcoholic Liver Diseases: Causes or Effects?. Gastroenterology. 2016;150(8):1745-1755.e3.