High Prevalence of Gut-Brain Interaction Disorders Found in Patients With Refractory Reflux Symptoms

A prospective study published in The American Journal of Gastroenterology has revealed that esophageal disorders of gut-brain interaction (E-DGBIs) are highly prevalent among patients with refractory reflux symptoms, including those with confirmed gastroesophageal reflux disease (GERD).

These findings underscore the need for careful diagnostic evaluation before considering interventional therapies in this challenging population.

The study enrolled 119 consecutive patients with typical reflux symptoms unresponsive to proton pump inhibitor (PPI) therapy. Patients were categorized based on results from pH monitoring, impedance studies, endoscopy, and manometry into 4 groups: proven GERD, unproven GERD, E-DGBI alone, and overlap of GERD with E-DGBI.

Among the 46 patients with confirmed GERD, only 13 (28%) had isolated refractory GERD. The majority—33 patients (72%)—had overlapping E-DGBIs. Similarly, among patients classified with unproven GERD, 68.5% had an E-DGBI. The overlap syndromes included functional dyspepsia (70.6%) and irritable bowel syndrome (33.6%), indicating a broader gastrointestinal involvement.

“E-DGBIs are highly prevalent in patients with proven GERD and refractory reflux symptoms,” the authors reported.

Symptom profiles, anxiety and depression scores, and visceral sensitivity did not significantly differ between those with isolated GERD and those with overlapping E-DGBIs. However, patients with confirmed refractory GERD had a higher acid exposure time and more reflux episodes compared to the GERD–E-DGBI overlap group, highlighting distinct pathophysiologic mechanisms.

These results challenge the assumption that persistent reflux symptoms are always due to uncontrolled acid reflux. “A higher acid exposure time and number of reflux episodes were found in patients with confirmed refractory GERD compared with the overlap E-DGBI-GERD group,” the study noted.

The authors emphasized the clinical importance of distinguishing E-DGBIs from acid-mediated GERD. “Studies with outcome data are needed to determine whether patients with overlapping E-DGBIs and GERD should be identified with pH-impedance monitoring on PPI therapy before an interventional treatment option is considered,” they concluded.

For gastroenterologists, these findings reinforce the need for a multidisciplinary diagnostic approach, including physiologic testing and psychosocial assessment, in patients with refractory reflux. Identifying E-DGBIs in this population may guide more effective, targeted management strategies and prevent unnecessary invasive procedures.

Reference
Caldart F, Gabriel C, Vauquelin B, Rivière P, Berger A, Zerbib F. Overlap of esophageal disorders of gut-brain interactions and gastroesophageal reflux disease is highly prevalent in patients with refractory reflux symptoms. Am J Gastroenterol. Published online May 22, 2025. doi:10.14309/ajg.0000000000003542