Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome

Abstract

Background: Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. Methods:We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires.Key Results: After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre-and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT. Conclusion and Inferences:This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.

Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models

“…We recently found that increased CH 4 on breath test correlated with increased abundance of methanogens, including M. smithii , in stool samples from IBS-C subjects, and predicted microbial metabolic pathway analysis indicated enrichment of pathways associated with methanogenesis in these subjects [ 6 ]. These findings are also consistent with an independent study which recently found that increased CH 4 on breath test was associated with slower oroanal transit times in IBS subjects, whereas increased H 2 on breath test was associated with more rapid oroanal transit times [ 11 ]. In the present study, increased stool M. smithii levels correlated with a constipation-like phenotype (decreased stool % wet weights) in a rat model.…”

“…In a recent publication, we identified distinct gut microbial compositions and associated breath gas profiles in subjects with IBS-C vs. IBS-D, with increased breath CH 4 in IBS-C subjects that correlated with increased levels of methanogens, including M. smithii , in stool samples, whereas IBS-D subjects had increased breath levels of both hydrogen (H 2 ) and hydrogen sulfide (H 2 S) [ 6 ]. A recent study by Algera et al, found that increased breath CH 4 levels were associated with decreased oroanal transit times in IBS subjects, and while that study did not measure H 2 S levels, they did find associations between increased breath H 2 levels and increased oroanal transit times in IBS [ 11 ]. The authors proposed that these findings resulted from differences in gut microbial compositions in different groups of IBS subjects [ 11 ], which is consistent with our identification of distinct gut microtypes and breath gas profiles in IBS-C vs. IBS-D subjects [ 6 ].…”

“…A recent study by Algera et al, found that increased breath CH 4 levels were associated with decreased oroanal transit times in IBS subjects, and while that study did not measure H 2 S levels, they did find associations between increased breath H 2 levels and increased oroanal transit times in IBS [ 11 ]. The authors proposed that these findings resulted from differences in gut microbial compositions in different groups of IBS subjects [ 11 ], which is consistent with our identification of distinct gut microtypes and breath gas profiles in IBS-C vs. IBS-D subjects [ 6 ]. Further, we found that increased breath H 2 S levels in IBS-D subjects correlated with increased abundances of H 2 S-producing bacterial species, including species from the genera Fusobacterium and Desulfovibrio , in stool samples [ 6 ], and microbial metabolic pathway analysis suggested enrichment of KEGG modules associated with methane production in CH 4 -positive IBS-C subjects, and enrichment of modules associated with H 2 S production in IBS-D subjects [ 6 ].…”

Low prevalence of positive hydrogen breath tests in patients with functional gastrointestinal conditions and hypermobile Ehlers–Danlos syndrome

“…Studies have shown that these patients have a much shorter oro-cecal transit time and hence a higher likelihood of having a false positive HBT. [38][39][40] This is due to the substrate reaching the cecum, before a higher exhaled hydrogen concentration is seen. Furthermore, many of the limitations of HBTs can be mitigated if they are combined with an independent measurement of orocecal transit (e.g., scintigraphy).…”

“…In our study, we found that patients who reported diarrhea and fluctuating bowel habit were more likely to have a positive HBT. Studies have shown that these patients have a much shorter oro‐cecal transit time and hence a higher likelihood of having a false positive HBT 38–40 . This is due to the substrate reaching the cecum, before a higher exhaled hydrogen concentration is seen.…”