High methane levels linked to refractory GERD

A significant association exists between refractory gastroesophageal disease (RGERD) and increased methane (CH₄) levels, reports a study.

Additionally, patients with RGERD may develop small intestinal bacterial overgrowth (SIBO) with long-term use of proton pump inhibitors (PPIs), and thus “interventions involving SIBO could provide new ideas for the treatment of RGERD,” the investigators said.

Patients with RGERD experienced a significantly greater incidence of acid reflux (67.1 percent vs 42.7 percent; p<0.01) and heartburn (65.0 percent vs 34.4 percent; p<0.01) than those with nonrefractory GERD (NRGERD). [J Clin Gastroenterol 2025;59:448-455]

At each time point, the CH₄ values were significantly greater in RGERD than NRGERD patients. CH₄ values at 60 min also showed an association with RGERD (p<0.05).

Moreover, the incidence of abdominal pain (61.9 percent vs 57.5 percent), acid regurgitation (69.05 percent vs 65.0 percent), and heartburn (69.05 percent vs 57.5 percent; p>0.05) was higher in CH₄-positive vs CH₄-negative RGERD patients. The same trend persisted for the incidence of nausea (61.9 percent vs 35.0 percent; p<0.05).

Mechanisms

There are several mechanisms that explain how SIBO promotes the occurrence and development of RGERD, according to the investigators. For instance, an increase in gas stimulates the vagus nerve-mechanical receptors, which then reduces the pressure of and relaxes the lower esophageal sphincter. 

Second, excessive gas widens the intercellular space, promotes acid-sensitive injury receptors, and elevates visceral sensitivity. This, in turn, results in acid reflux, abdominal pain, and other symptoms.

Increased intestinal gas can also elevate intra-abdominal pressure, leading to the reflux of gastric contents into the esophagus and causing mucosal damage to extraesophageal organs, including the larynx, oral cavity, nasal cavity, and trachea.

Furthermore, “[hydrogen] and CH₄ can significantly reduce intestinal pressure and reduce the phase III contraction amplitude of the transitional motor complex (MMC) during the interdigestive period, thereby affecting the speed of intestinal food propulsion and further increasing the production of H₂ and CH₄ in the intestine, thus forming a vicious cycle,” the investigators said.

Finally, CH₄ has the capacity to lower the concentration of blood 5-hydroxytryptamine, which is secreted by intestinal chromaffin cells and is a significant signalling molecule involved in the regulation of gastrointestinal movement and perception.

“In addition to the above physiological effects, due to recurrent symptoms, difficulty in relieving symptoms, and repeated medical treatment, most patients with RGERD have varying degrees of anxiety and depression,” the investigators said.

Psychological effect

“SIBO can also induce mental and psychological disorders such as anxiety and depression by damaging the brain–gut axis to the central nervous system,” they added.

Subsequently, anxiety and depression can both induce lower esophageal sphincter relaxation and delayed gastric emptying. This results in worse reflux symptoms and sensitivity to such symptoms in patients, causing them to deteriorate further. [J Neurogastroenterol Motil 2018;24:593-602; Chin J Microecol 2022;34:489-492]

“In this study, the rate of SIBO positivity and the incidence of esophageal symptoms such as acid reflux and heartburn in the RGERD group were greater than those in the NRGED group, which supports previous research results,” the investigators said. 

A total of 178 patients with GERD were enrolled in this study from June 2020 to December 2022. Of these, 96 had NRGERD and 82 had RGERD. The investigators collected the Gerd Q score, reflux symptom index score, gastroscopy results, clinical symptoms, and other related indicators. They analysed the obtained data using statistical methods.