S500 Presence of Methane in the Fasting Breath Is Associated With a Lower Rise in Pancreatic Polypeptide After Modified Sham-Feeding: An Insight into the Connection Between Vagal Dysfunction and Methane

Abstract

Introduction: The vagus nerve as a key part of the parasympathetic system regulates gut motility and is implicated in numerous diseases. Pancreatic Polypeptide modified sham-feeding test (PP MSF) is an indirect method to measure vagal tone by measuring serum pancreatic polypeptide levels after chewing but not swallowing food (Balaji et al. JAMA surgery 2002). Excess intestinal methane (CH4) is associated with constipation and is thought to act as a gasotransmitter via the cholinergic pathway. We aimed to evaluate the association between fasting exhaled CH4 and vagal dysfunction as measured by the PP MSF. Methods: Utilizing a natural-language processor, patients with a lactulose breath test (LBT) and PP MSF were identified from Jan 2010 to Oct 2020. Patient demographics, medical history known to affect vagal dysfunction, and a history of esophagectomy or fundoplication were collected. For LBT, patients were asked to eat a low-fermentable diet and fasted for 12 hours prior to the test. Baseline (fasting) CH4 measurements corrected to breath CO2 levels were collected for this study. For the PP MSF, patients fasted for 12 hours then were asked to chew and spit out a hamburger without swallowing. Serum PP levels were measured before and after MSF in 5-minute intervals for 30 minutes. Percent rise in PP from baseline were calculated and compared between patients that had detectable (CH4 > 0 ppm) vs undetectable (CH4 = 0 ppm) CH4 on their baseline LBT. Results: Forty-three patients (27.9% males, median age = 51 ± 17.8 years) were included in the cohort. Eighteen patients (41.8%) had detectable fasting CH4 (median CH4 = 3.0 ± 12.4 ppm). There was no difference in baseline characteristics or prespecified risk factors affecting vagal dysfunction between those who had detectable and undetectable CH4 (Table 1). Patients with CH4 had a significantly lower rise in PP after MSF (4.9% ± 49.0 vs 42.2% ± 96.1, p = 0.01) (Figure 1). Subgroup analysis for patients without esophagectomy or fundoplication showed that detectable CH4 is associated with numerically lower rise in PP (13.4% ± 38.0 vs 39.6% ± 49.9, p = 0.07). Conclusion: This is the first study to show that a detectable CH4 in the breath is associated with a lower rise in PP MSF. We hypothesize that CH4 may be altering vagal tone by affecting the cholinergic pathway. Mechanistic animal models and prospective human studies without esophagectomy or fundoplication are needed to confirm these findings.Table 1.: Demographics and Characteristics of Patients with Constipation*. *The baseline period was defined as the 6 months before the index date; †Includes lubiprostone, linaclotide and plecanatide. CIC, chronic idiopathic constipation; SD, standard deviation.Figure 1.: a) Patients with CH4 had significantly lower rise in PP than those without CH4. b) Mean PP levels plotted over time. Percent rise was significantly lower in patients with detectable CH4 (42.2% vs 4.9%, p = 0.01). PP = pancreatic polypeptide, CH4 = methane.