Can bile salts affect the contractile oesophageal activity associated with gastroesophageal reflux disease?

Bile salts are essential molecules that have evolved beyond their digestive surfactant properties to act as relevant pathophysiological signalling modulators. In the gastroesophageal reflux disease (GERD), recurrent exposure of the oesophagus to harmful agents of gastric and duodenal origin, including bile salts, results in chronic inflammation and damage to the oesophageal mucosa, ultimately promoting the progression of the normal oesophageal epithelium to pre-malignant or malignant lesions, such as Barrett's oesophagus and adenocarcinoma. Although the acidity of the refluxed material has long been considered the leading cause of pathological features in GERD, some patients do not respond adequately to conventional therapy with proton pump inhibitors, implicating non-acidic components of the gastroesophageal reflux originating in the stomach and/or duodenum. Oesophageal motor activity is an essential protection against GERD symptoms, as it directly determines the contact time of the refluxed material inside the oesophagus. Oesophageal dysmotility profiles are documented in GERD, and bile salts appear to contribute to this dysfunction. In this work, we highlight the involvement of bile salts in the pathogenesis of GERD, particularly their effect on oesophageal motility and their potential signalling pathways.