Figure 1. Barrett’s specialized intestinal metaplasia and mucosal defense.

Barrett’s metaplasia arises in an environment of chronic reflux in which the distal esophagus is exposed to high levels of local and systemic damage from acid, bile, and tobacco products as well as the inflammatory responses to the injury(12, 55-60). All are mutagenic. Barrett’s metaplasia has a number of defenses against this mutagenic environment that are not found in esophageal squamous epithelium(12, 43). A. Barrett’s metaplasia secretes anions, including bicarbonate, that participate in buffering acid reflux (61). B. Barrett’s metaplasia is a well differentiated epithelium with crypt architecture in which putative stem cells residing at the base give rise to proliferating transient amplifying cells and differentiated cells that are sloughed into the lumen. This architecture has been proposed to be tumor suppressive because mutations in transient amplifying or differentiated non-stem cells would be shed from the body before they could accumulate the serial mutations that lead to cancer(62). C Barrett’s metaplasia secretes a thick adherent mucus not present in squamous esophageal epithelium for defense against acid and bile reflux(45, 46, 63)(64). D. Barrett’s esophageal cells maintain physiological intracellular pH following prolonged and repeated reflux exposure(65). E. The tight junctions of Barrett’s metaplasia overexpress claudin 18 and several other claudins, including 1, 4, 12 and 23, that provide protection against acid permeation(66). F. A combined expression and proteomics study of Barrett’s metaplasia reported overexpression of genes involved in mucosal defense and repair(44).