The noxious agents responsible for injuring the oesophageal mucosa in patients with gastro-oesophageal reflux disease (GORD) may originate from two possible sources, the stomach and the duodenum. Hydrochloric acid and pepsin are the important gastric contents, whereas conjugated and unconjugated bile acids and trypsin are the proposed duodenal ingredients predisposing to the development of oesophageal symptoms and mucosal injury.1 The regurgitation of these duodenal contents into the stomach followed by reflux into the oesophagus is known as duodenogastro-oesophageal reflux (DGOR).

To date, the controversy in the literature regarding the specific agents responsible for oesophageal damage centres around the relative importance of acid/pepsin reflux versus DGOR. Early animal studies have clearly shown that acid alone, and in combination with various pepsin concentrations, is damaging to the oesophagus.2-5 For example, Goldberg and colleagues2 showed oesophageal mucosal damage in the intact feline oesophagus with either very high acid concentrations (pH 1.0–1.3) or lower acid concentrations (pH 1.6–2.0) in the presence of pepsin. Additionally, human studies3-5 have clearly delineated a positive correlation between the degree of abnormal acid reflux and the severity of oesophagitis. These studies show that more than 90% of patients with oesophagitis and Barrett’s oesophagus have increased oesophageal exposure to acid on pH monitoring.5 Additionally, Bremner and colleagues6 observed that patients with increased oesophageal exposure to pH 1–2, corresponding to the known pKa of pepsin, had the most significant degrees of oesophagitis; an indirect inference to the possible importance of pepsin. Therefore, the role of acid and pepsin in causing oesophageal mucosal injury is irrefutable.

The role of duodenal contents in the development of oesophageal mucosal injury is controversial and the subject of many animal and human studies. Animal studies show that oesophageal mucosal damage caused by bile acids is …