Antimicrobial proteins: intestinal guards to protect against liver disease

Abstract

Alterations of gut microbes play a role in the pathogenesis and progression of many disorders including liver and gastrointestinal diseases. Both qualitative and quantitative changes in gut microbiota have been associated with liver disease. Intestinal dysbiosis can disrupt the integrity of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the liver. In order to sustain symbiosis and protect from pathological bacterial translocation, antimicrobial proteins (AMPs) such as a-defensins and C-type lectins are expressed in the gastrointestinal tract. In this review, we provide an overview of the role of AMPs in different chronic liver disease such as alcoholic steatohepatitis, non-alcoholic fatty liver disease, and cirrhosis. In addition, potential approaches to modulate the function of AMPs and prevent bacterial translocation are discussed.

Keywords: Bacterial translocation; Dysbiosis; Innate immune system; Microbiome.

Fig. 1

Steatosis (fatty liver) due to obesity (diet), alcohol consumption, other environmental or genetic factors is associated with dysbiosis, loss of intestinal tight junctions, reduced intestinal epithelial integrity, increased permeability and lower expression of antimicrobial proteins (AMPs). This allows bacterial products such as LPS (via the paracellular route) or viable bacteria (via not further detailed mechanisms) to translocate into the bloodstream and mesenteric lymph nodes. Via the portal vein, bacteria and their products reach the liver, where they promote progression to more severe stages of liver disease via recognition by Toll-like receptors (TLRs) on Kupffer cells, hepatic stellate cells and hepatocytes, leading to inflammation, fibrosis and cell death (Figure made using Servier Medical Art; http://smart.servier.com)