Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

Abstract

Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora.

The Gut-Liver Axis in Cholestatic Liver Diseases

“…A connection between gut and liver seems to be obvious in PSC due to the common appearance of IBD in PSC patients and the fact that prior colectomy before liver transplantation decreases the risk of PSC recurrence in the donor liver [ 88 , 89 ]. The IBD-PSC phenotype clinically often presents with an atypical mild right-sided colitis with rectal sparing and backwash ileitis, suggesting a distinct phenotype of the disease [ 90 , 91 , 92 ]. Increased paracellular permeability, associated with genetic variants of the nucleotide-binding oligomerization domain-containing protein 2 (NOD2), in both CD and UC have been shown [ 93 , 94 , 95 , 96 ].…”

“…Dysbiosis of the gut microbiome, characterized by an imbalance of microbes, as trigger for the evolution and progression of liver diseases is an accepted pathophysiological concept. As pointed out already, dysbiosis influences the gut barrier and bile acid composition and leads to fibrosis and cirrhosis [ 91 , 121 ]. Furthermore, dysbiosis also takes part in the promotion of carcinogenesis of hepatocellular cancer [ 177 ].…”

“…Furthermore, dysbiosis also takes part in the promotion of carcinogenesis of hepatocellular cancer [ 177 ]. Alterations of the microbiome have been shown for cholestatic liver diseases, but also for alcohol-induced liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), drug-induced liver injury, viral-induced liver diseases, and cirrhosis [ 8 , 27 , 91 , 178 ]. The question always arises when dealing with description of microbiome alterations in various diseases: Are changes in the microbiome the cause or the consequence of the disease?…”

Novel pathomechanism for spontaneous bacterial peritonitis: disruption of cell junctions by cellular and bacterial proteases

“…We know that bacterial translocation (BT)-with Escherichia coli (E. coli), Klebsiella pneumoniae and streptococci being the most common microbes-from the gut to mesenteric lymph nodes is crucial for the development of SBP. [7][8][9] BT is driven by a suppressed intestinal immune system with small intestinal bacterial overgrowth and reduced microbial diversity. 8 10-14 In addition, increased permeability of the intestinal…”

Nonalcoholic fatty liver disease and alcohol-related liver disease: From clinical aspects to pathophysiological insights

“…Chronic alcohol exposure, as well as dietary overload, compromises gut barrier function causing increases in intestinal permeability, thereby aggravating translocation of bacterial products into the portal blood. 51 Pathogen-associated molecular patterns (PAMPs) derived from gut microbiota elicit production and release of inflammatory cytokines through multiple innate immune-signaling pathways, resulting in the exacerbation of steatohepatitis. 52 We investigated the alteration in the small intestinal microbiota profile following chronic EtOH feeding in KK-A y mice, and the effect of rifaximin (RFX) on liver injury following chronic/binge administration of EtOH.…”