About the study
The June 2012 Issue of Annals of Surgery contains a published study reporting that Barrett’s esophagus, which develops in approximately 5 to 8 percent of patients with GERD, may be the result of bile reflux rather than stomach acid. The study was conducted by a team of scientists at the University of Rochester (New York) Medical Center – whose lead study author, Jeffrey H. Peters, M.D., is the Professor and Chairman of the Department of Surgery – as well as scientists from the Ontario Institute for Cancer Research in Toronto and the Pittsburgh Cancer Institute at the University of Pittsburgh. The aim of the study was to better understand how and why Barrett’s esophagus occurs from a biological perspective. When people are diagnosed with Barrett’s esophagus, this means that the normal lining of the esophagus (a skin-like tissue referred to as squamous epithelium) has changed to tissue more closely characteristic of the lining of the intestine (columnar epithelium). The researchers report that the change from squamous to columnar, which is controlled by a complex of genes is not influenced by gastric acid; rather it is influenced by bile derivatives. The importance of these findings is the fact that most medications in the market for treating GERD suppress gastric acid.
What are bile acids?
Bile acids are produced by the liver, stored in the gallbladder, and released into the upper part of the small intestine (called the duodenum) to aid digestion of fats in the food. Reflux of duodenal contents, which are alkaline and include bile acids, into the stomach occurs commonly and is the result of failure of the pyloric valve, the muscular ring between the stomach and the small intestine. If reflux of gastric contents into the esophagus occurs in a person who also has duodeno-gastric reflux, bile that has entered the stomach from the upper small intestine can accompany stomach acid into the esophagus.
There is evidence that the presence of bile acids in gastric contents contributes to the damage caused in the squamous epithelial lining of the esophagus. In particular, it has been shown that patients who have Barrett’s esophagus have a greater likelihood of having duodeno-gastro-esophageal reflux. In these patients, it is believed that bile is a potent promoter of the transformation of squamous to columnar epithelium and in particular to a specific type of columnar epithelium that is Barrett’s esophagus. The importance of this specific intestinal type of columnar epithelium is that it is known to be premalignant.
The University of Rochester study provides a genetic basis for the role of bile in promoting columnar (and intestinal) metaplasia in the esophagus. According to the researchers and Dr. Peters, bile suppresses genes involved in maintaining the esophageal epithelium as squamous and activates genes that cause columnar transformation of the squamous epithelium. In contrast, acid does not suppress genes that maintain squamous epithelium or activate genes that promote columnar metaplasia.
Why is bile reflux important?
The importance of this finding is that it provides further evidence that treating GERD with acid suppressive drugs, while controlling symptoms, does not prevent conversion of the squamous lining of the esophagus to the columnar (intestinal type) lining that signifies Barrett’s esophagus. The epithelial change that is associated with cancer is not prevented by PPI therapy. This would explain why treatment of GERD with PPIs and other acid suppressive agents has been associated with an increasing incidence of both Barrett’s esophagus and reflux-induced adenocarcinoma in the past five decades. If bile and not acid is the culprit for generating Barrett esophagus and cancer, treating GERD with PPIs is not addressing the cause of these conditions.