Methanogens, Methane and Gastrointestinal Motility

Anaerobic fermentation of the undigested polysaccharide fraction of carbohydrates produces hydrogen in the intestine which is the substrate for methane production by intestinal methanogens. Hydrogen and methane are excreted in the flatus and in breath giving the opportunity to indirectly measure their production using breath testing. Although methane is detected in 30%-50% of the healthy adult population worldwide, its production has been epidemiologically and clinically associated with constipation related diseases, like constipation predominant irritable bowel syndrome and chronic constipation. While a causative relation is not proven yet, there is strong evidence from animal studies that methane delays intestinal transit, possibly acting as a neuromuscular transmitter. This evidence is further supported by the universal finding that methane production (measured by breath test) is associated with delayed transit time in clinical studies. There is also preliminary evidence that antibiotic reduction of methanogens (as evidenced by reduced methane production) predicts the clinical response in terms of symptomatic improvement in patients with constipation predominant irritable bowel syndrome. However, we have not identified yet the mechanism of action of methane on intestinal motility, and since methane production does not account for all constipation associated cases, there is need for high quality clinical trials to examine methane as a biomarker for the diagnosis or as a biomarker that predicts antibiotic treatment response in patients with constipation related disorders.

Recorded Lower Esophageal Pressures as a Function of Electronic Sleeve Placement and Location of Gastric Pressure Measurement in Patients With Hiatal Hernia

BACKGROUND/AIMS: In high-resolution manometry lower esophageal sphincter pressure (LESP) is measured relative to intragastric pressure, however Gastric Marker(TM) (GM) location used to determine resting LESP is not well established with hiatal hernia (HH). We test the hypothesis that measured resting LESP varies with HH based on GM location. METHODS: Subjects with HH > or = 2 cm were included. The eSleeve(TM) was adjusted to span only the LES, excluding the crural diaphragm (CD). Resting LESP was determined by placing the GM below and above the CD (in the position yielding the highest resting LESP). Resting pressure across the lower esophageal sphincter (LES) to CD and pressure in the HH relative to subdiaphragmatic intragastric pressure were also measured. RESULTS: HH > or = 2 cm was present in 98 patients (mean length 2.7 cm). LESP decreased when GM was moved from below the CD into the HH: respiratory minimum LESP 7.5 +/- 1.1 to 3.6 +/- 0.9 mmHg; P < 0.001, mean LESP 17.7 +/- 1.3 to 13.7 +/- 1.1 mmHg; P < 0.001. When the eSleeve encompassed the LES and CD, the respiratory minimum pressure was 12.2 +/- 0.9 mmHg and mean pressure was 23.9 +/- 1.0 mmHg pressure (P < 0.001 for both). Pressure in the hernia pouch was greater than intragastric pressure: respiratory minimum 3.0 +/- 0.7 mmHg and mean 9.0 +/- 0.8 mmHg (P < 0.001 for both). pH studies showed a trend toward an association between abnormal distal esophagus acid exposure and lower resting LESP. CONCLUSIONS: GM placement in the HH produces lower resting LESPs. This may provide a more physiologic representation of LESP in HH.

Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome

BACKGROUND/AIMS: Campylobacter jejuni infection is a leading cause of acute gastroenteritis, which is a trigger for post-infectious irritable bowel syndrome (PI-IBS). Cytolethal distending toxin (CDT) is expressed by enteric pathogens that cause PI-IBS. We used a rat model of PI-IBS to investigate the role of CDT in long-term altered stool form and bowel phenotypes. METHODS: Adult Sprague-Dawley rats were gavaged with wildtype C. jejuni (C+), a C. jejuni cdtB knockout (CDT-) or saline vehicle (controls). Four months after gavage, stool from 3 consecutive days was assessed for stool form and percent wet weight. Rectal tissue was analyzed for intraepithelial lymphocytes, and small intestinal tissue was stained with anti-c-kit for deep muscular plexus interstitial cells of Cajal (DMP-ICC). RESULTS: All 3 groups showed similar colonization and clearance parameters. Average 3-day stool dry weights were similar in all 3 groups, but day-to-day variability in stool form and stool dry weight were significantly different in the C+ group vs both controls (P < 0.01) and the CDT- roup (P < 0.01), but were not different in the CDT- vs controls. Similarly, rectal lymphocytes were significantly higher after C. jejuni (C+) infection vs both controls (P < 0.01) and CDT-exposed rats (P < 0.05). The counts in the latter 2 groups were not significantly different. Finally, c-kit staining revealed that DMP-ICC were reduced only in rats exposed to wildtype C. jejuni. CONCLUSIONS: In this rat model of PI-IBS, CDT appears to play a role in the development of chronic altered bowel patterns, mild chronic rectal inflammation and reduction in DMP-ICC.

Estimating the Contribution of Acute Gastroenteritis to the Overall Prevalence of Irritable Bowel Syndrome

BACKGROUND/AIMS: Recent studies reveal that acute gastroenteritis can precipitate irritable bowel syndrome (IBS) symptoms leading to the concept of post-infectious IBS. However, the overall contribution of gastroenteritis to the total IBS prevalence is unknown. In this exercise we try to estimate the contribution of gastroenteritis in IBS using the published literature and a longitudinal approach. METHODS: Existing literature was reviewed to determine the incidence of IBS after gastroenteritis, the rate of remission over time, data on rates of gastroenteritis in a given population and any patterns of resistance to these effects in human populations. This produced 3 models. The first assumed all humans were susceptible to gastroenteritis and its ability to produce IBS. The second assumed (using meta-analysis data) that 90% of humans in a given outbreak would be resistant to this effect. The third model used a high gastroenteritis exposure rate as might be seen in military deployment. RESULTS: In model 1, the prevalence was unrealistically high with an eventual steady state of 43.6% of the population affected by IBS. In a very conservative approach (model 2), steady state was achieved after 10 years to an overall prevalence of 8.9%. Interestingly, based on a high 1 year exposure rate such as military deployment, the maximum prevalence (steady state) was reached before 1 year suggesting high risk. CONCLUSIONS: Although hypothetical in approach, based on conservative estimates in existing literature the contribution of gastroenteritis to the overall prevalence of IBS is substantial.

PILL series. What is my ideal diabetes target?

Diabetes mellitus is common in our increasingly affluent and ageing population. Although it is an old friend of practising family physicians, there is a need to be familiar with and up to date about the disease. As patients become more informed and receptive to current medical information, family physicians also need to stay current. This article highlights the evidences that have shaped our current treatment targets for type 2 diabetes mellitus.