Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria?

Figure 1 Environmental factors alter the local esophageal microbiome, which normally has a gram-positive to gram-negative gradient, towards increased proportion of gram-negatives. Activation of Toll-like-receptor-4 by gram-negative lipopolysaccharide leads towards an inflammatory cascade that results in lymphocyte infiltration. In addition, gastric acid activates transient receptor potential cation channel subfamily V member 1 on local nerve fibers and results in calcitonin gene-related peptide and substance P expression, which contributes to the local inflammatory response as well as pain. LPS: Lipopolysaccharide; TLR: Toll-like-receptor; NF-κB: nuclear factor-kappa beta; IFN: Interferon; ROS: Reactive oxygen species; TRPV1: Transient receptor potential cation channel subfamily V member 1; CGRP: Calcitonin gene-related peptide.