The Influence of the Gut Microbiome on Obesity, Metabolic Syndrome and Gastrointestinal Disease

Abstract

There is a fine balance in the mutual relationship between the intestinal microbiota and its mammalian host. It is thought that disruptions in this fine balance contribute/account for the pathogenesis of many diseases. Recently, the significance of the relationship between gut microbiota and its mammalian host in the pathogenesis of obesity and the metabolic syndrome has been demonstrated. Emerging data has linked intestinal dysbiosis to several gastrointestinal diseases including inflammatory bowel disease, irritable bowel syndrome, nonalcoholic fatty liver disease, and gastrointestinal malignancy. This article is intended to review the role of gut microbiota maintenance/alterations of gut microbiota as a significant factor as a significant factor discriminating between health and common diseases. Based on current available data, the role of microbial manipulation in disease management remains to be further defined and a focus for further clinical investigation.

Figure 1

Gut microbiota and its influence on obesity.

Figure 2

Gut microbiota and its influence on nonalcoholic fatty liver disease and nonalcohlic steatohepatitis. Proposed mechanisms, working individually or in concert, by which intestinal dysbiosis results in nonalcoholic fatty liver disease and nonalcohlic steatohepatitis. Interaction between lipopolysaccharide and SIBO/CD14 upregulates pro-inflammatory cytokines resulting in increased permeability and inflammation. Bacterial translocation (from SIBO) occurs in lieu of increased permeability activating the innate immune response resulting in a pro-inflammatory state. Intestinal dysbiosis results in production of enzyme that catalyzes choline into toxic methylamines that are injurious to the host liver.

Figure 3

Gut microbiota and its influence on esophageal adenocarcinoma. Type-microbiota (Gram-positive predominant) with H. pylori provides a neutral esophageal environment. Type-II microbiota (Gram-negative predominant) with loss of H. pylori invokes a pro-inflammatory state in two ways. First, loss of H. pylori allow for increased acid secretion resulting in gastroesophageal reflux disease and its sequelae. Second, predominance of Gram-positive bacteria upregulate the pro-inflammatory cascade due to the interaction between lipopolysaccharide and Toll-like receptor 4.