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#Gastroenterology #Hepatology #Multispeciality
Changes in the intestinal microbiota composition play an important role in the pathogenesis of many disorders including gastrointestinal and liver diseases. Evidence based observations have focussed on the wide spectrum of the “gut-liver” axis. Various factors such as dietary changes, environmental and genetic factors can cause alterations in the microbiota. Dysbiosis also alters the integrity of the intestinal barrier causing pathological bacterial translocation and the initiation of an inflammatory response in the liver.
Evidences demonstrated that deficiency of the major inflammasome component NLRP6 can cause intestinal dysbiosis. Inflammasomes are cytosolic multiprotein complexes, which respond to microbial products or alteration of cellular physiology and are known to activate caspase-1, which break down proinflammatory cytokines pro-interleukin (IL)-1β and pro-IL-18 into their active forms. This effector cytokine IL-18 instead of IL-1β is regarded responsible for intestinal dysbiosis.
Additionally, the abnormal microbiota can induce colonic inflammation via the induction of chemokine (C-C motif) ligand (Ccl5) from epithelial cells, which in turn includes a various innate and adaptive immune cells which then promotes inflammation. This inflammation results in translocating of toll-like receptor (TLR) agonists including lipopolysaccharide (LPS) and bacterial DNA to the portal vein and liver. These microbial products then bind to TLR4 and TLR9 in the liver and trigger downstream signaling that improves the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). The increased innate immune signaling in the liver via TLRs also contributes in the progression of other liver diseases including alcoholic liver disease, liver fibrosis and chronic viral hepatitis.
Other factors that cause alterations in the composition of microbiota involve dietary factors. Several studies demonstrated that chronic alcohol consumption results in qualitative and quantitative changes of the microbiota. Qualitative changes involves a reduction in Firmicutes such as Lactobacillus and an increase in Bacteroidetes following alcohol exposure in experimental test. Similar fndings have been corroborated by another study that reported a decrease in Bifidobacterium and Lactobacillus in the stool of alcohol-dependent individuals. Moreover, researchers abstinence of alcohol has the ability to suppress Lactobacillus ssp. and Bifidobacterium ssp., suggestive of the fact that bacteria have beneficial effects and can play a role in the recovery process of the intestinal tract.
Some researches demonstrated that alcohol consumption to experimental animals results in the decreased capacity of the intestinal bacteria to produce saturated long-chain fatty acids (LCFA), which contribute in maintaining eubiosis and for preventing overgrowth of intestinal bacteria. The presence of LCFA is associated with intestinal levels of beneficial lactobacilli in alcoholics, which are essential for maintaining the integrity of the intestinal barrier.
Therefore, dysbiosis induced by environmental factors, dietary changes or genetic components can result in intestinal inflammation, which along with hepatic injury can result in progression of liver disease.
Source: Brandl K, Schnabl B. Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease?. Expert Rev Gastroenterol Hepatol. 2015;9(8):1069-1076.