Figure 2.

Simplified model of intestinal Stages in the development of nonalcoholic fatty liver disease (NAFLD) and ways probiotics can intervene. Adverse environmental, metabolic and genetic factors such as diet rich in fat or fructose can cause intestinal dysbiosis with reduction of beneficial bacteria and increase of deleterious bacteria. Dysbiosis results in increased intestinal permeability, or “leaky gut”, by disruption of tight junction proteins such as zonula occludens‐1 and occludin. Associated metabolic changes in the bacteria lead to ‐ amongst others ‐ depletion of choline (which is metabolized to trimethylamine [TMA]), and production of ethanol (EtOH). EtOH and microbial products, e.g. lipopolysaccharides (LPS), translocate from the intestine into the blood circulation and travel to the liver. In the liver, choline deficiency promotes steatosis, and EtOH and LPS cause more liver inflammation and finally NAFLD/nonalcoholic steatohepatitis (NASH). Probiotics (living non‐pathogenic microorganisms such as Lactobacilli and Bifidobacteria that have a favorable impact on the host) work on several levels. They attenuate intestinal dysbiosis and metabolic changes, and ameliorate the “leaky gut” by preventing inflammation and apoptosis of the enterocytes, and by inducing tight junction proteins. Probiotics thereby decrease translocation of bacterial products and metabolites into the blood stream, which eventually alleviates liver injury. Abbreviations: EtOH, ethanol; LPS, lipopolysaccharide; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; TMA, trimethylamine.