Will Takakura, MD1, Christine Chang, RN2, Ava Hosseini, BS2, Jiajing Wang, MS2, Edward Kowalewski2, Ruchi Mathur, MD, FRCP(C)3, Ali Rezaie, MD, MSc2, Mark Pimentel, MD, FRCP(C)3; 1Cedars-Sinai, Los Angeles, CA; 2Cedars-Sinai Medical Center, Los Angeles, CA; 3Medically Associated Science & Technology, Cedars-Sinai Medical Center, Los Angeles, CA
Introduction: Although the gut microbiome has been known to influence many organs, few have evaluated its role in regulating the host’s vital signs. Methane (CH4) (produced by intestinal archaea) is believed to be a gasotransmitter as it affects intestinal smooth muscle causing constipation. However, its systemic effects are less known. Here we present the first study to describe the relationship between CH4 and cardiovascular related vital signs. Methods: Lactulose breath tests (BTs) were performed between Nov 2005 and Oct 2013. After a 12 hour fast, subjects were asked to ingest 10 g of lactulose and BT samples were collected every 15 minutes for at least 2 hours. BT samples were analyzed for hydrogen (H2) and CH4 after correcting for exhaled carbon dioxide. Small intestinal bacterial overgrowth (SIBO) was defined as H2 increase by 20 ppm by 90 minutes, intestinal methanogen overgrowth (IMO) was defined as CH4 ≥ 10 ppm. CH4 AUC was calculated by totaling the CH4 produced in the first 90 minutes. The closest heart rates (HR) and systolic/diastolic blood pressures (SBP/DBP) prior to the BT were analyzed. Results: Of 14,847 BT subjects, 1386 and 1795 subjects had their HR and BP readings available for analysis. The median ± SD difference in the days between the vital sign readings and the breath test dates were 218 ± 358 and 276 ± 461 days for HR and BP, respectively. HR was significantly lower in subjects with IMO compared to patients with H2 SIBO and Normal BT (p=0.002 and p=0.03), and there was no statistically significant difference for SBP or DBP (Figure 1). When subjects were grouped into those with CH4 ≥ 10 ppm or < 10 ppm, subjects with CH4 ≥ 10 ppm had a lower median HR than subjects with CH4 < 10 ppm (Figure 2). No difference in BP were seen. A decrease in HR was significantly associated with an increase in CH4 AUC (R=-0.07, p=0.008) and maximum CH4 (R=-0.07, p=0.005). In a multivariable regression analysis adjusted for age, sex and the difference in days from the HR readings and the BT dates, CH4 ≥ 10 ppm was significantly associated with HR (OR=0.988 95%CL 0.977-0.998, p=0.02) and age (OR=1.014 95%CL 1.006-1.022, p=0.0007). Discussion: Patients with excessive CH4 have modest but significantly lower HR. Furthermore, there appears to be a biological gradient with higher levels of CH4 being associated with lower HR. Future mechanistic studies are warranted to investigate the suppression of HR due to methanogenesis.
Figure 1. Shows median ± standard error HR, SBP , and DBP by different breath test results. Subjects with IMO had significantly lower HR then subjects with a normal BT (p = 0.03) or H2 SIBO (p = 0.002). * denotes p<0.05. sample size is labeled above each bar. IMO = intestinal methanogen overgrowth, BT = breath test, SIBO = H2 small intestinal bacterial overgrowth.
Figure 2. Shows median ± standard error HR, SBP , and DBP. Cohort was divided into groups of CH4 ≥ 10 ppm vs < 10 ppm. Subjects with CH4 ≥ 10 ppm had significantly lower HR than those with CH4 < 10 ppm (p = 0.005). * denotes p<0.05. Sample size is labeled above every bar.
Disclosures: Will Takakura indicated no relevant financial relationships. Christine Chang indicated no relevant financial relationships. Ava Hosseini indicated no relevant financial relationships. Jiajing Wang indicated no relevant financial relationships. Edward Kowalewski indicated no relevant financial relationships. Ruchi Mathur indicated no relevant financial relationships. Ali Rezaie: Bausch Health – Consultant, Grant/Research Support, Speaker's Bureau. Gemelli Biotech – Stockholder/Ownership Interest (excluding diversified mutual funds). GutHub – Consultant. Synthetic Biologics – Grant/Research Support. Mark Pimentel indicated no relevant financial relationships.