Alteration of sulfate and hydrogen metabolism in the human colon by changing intestinal transit rate

OBJECTIVES: Changes in intestinal transit rate are also implicated in the etiology of many colonic diseases and strongly influence many metabolic processes in the colon. We set out to investigate whether intestinal transit time could influence the activity of the hydrogen-consuming bacterial flora and sulfate metabolism. METHODS: Normal volunteers underwent four interventions while taking a low-sulfate diet: placebo, sulfate supplements, or sulfate supplements with either senna or loperamide. Stools were cultured and analyzed for sulfate, sulfide, methionine, sulfate reduction rates, methionine reduction rates, acetic acid production rates, methane production rates, short-chain fatty acids, and bile acids. Urine was analyzed for sulfate. RESULTS: The addition of sulfate alone increased fecal and urinary excretion of sulfate, fecal sulfide, sulfate reduction rates, and acetic acid production rates; it reduced fecal methanogenic bacterial concentrations. Faster intestinal transit increased fecal sulfate, sulfide, bile acids, the reduction rates of sulfate, and methionine and the production rates of acetic acid. Reduction in fecal methanogens and methane production was seen. The reverse effects were seen with loperamide. CONCLUSIONS: Both sulfate supplements and changes in intestinal transit rate markedly alter the activity of the colonic bacterial flora with respect to sulfate metabolism and hydrogen disposal. Dietary influences on intestinal transit and sulfate consumption may influence disease processes. While a variety of processes govern sulfate metabolism and hydrogen disposal, our knowledge is far from complete. How far the observed changes in sulfate metabolism seen in certain diseases are relevant to the pathogenesis of the disease or secondary to the disease itself is unclear.     

Stability of human methanogenic flora over 35 years and a review of insights obtained from breath methane measurements.

BACKGROUND & AIMS: Breath methane measurements reflect the in situ activity of the methanogenic colonic flora. Thirty-five years ago we found that 34% of healthy adult subjects were methane producers (breath methane level >1 ppm above atmospheric methane levels). The current study presents a new survey of breath methane levels designed to determine if the activity of the methanogenic flora has changed over the past 35 years. In addition, we review insights into the methanogenic flora that have resulted from breath methane measurements. METHODS: The end-alveolar breath methane concentrations of 212 healthy adults living in the Minneapolis area were determined via gas chromatography. The influence of sex, age, and bowel movement frequency on methane production was assessed. RESULTS: The findings that 36.4% of participants were methane producers, with a mean methane concentration in these producers of 16.6 ppm, are strikingly similar to the values of 33.6% and 15.2 ppm observed 35 years ago. Neither sex nor age showed a statistically significant relationship to methane production. There was a negative correlation between frequency of bowel movements and breath methane concentration in methane producers. CONCLUSIONS: The activity of the methanogenic flora of healthy adults remained remarkably stable over the past 35 years despite widespread antibiotic use and dietary changes. A literature review revealed that many associations have been shown between methane production and clinical states, but it remains to be determined if methanogens actively influence human physiology or are simply a marker of colonic function.     

Incidence of Predominant Methanogenic Flora in Irritable Bowel Syndrome Patients and Apparently Healthy Controls from North India

Background Flatulence is a common symptom in patients with irritable bowel syndrome (IBS). This may be due to production of hydrogen by intestinal flora. With the presence of methanogenic flora, 4 mol of hydrogen (H₂) are used with 1 mol of carbon dioxide (CO₂) to produce 1 mol of methane (CH₄), a process greatly reducing the volume of gas in the colon. However, the prevalence of methanogenic flora has not yet been reported in healthy and IBS patients from North India. Therefore, this study was planned. Methods This study was conducted prospectively and included 345 patients with irritable bowel syndrome (fulfilling Rome II criteria) and 254 age- and gender-matched apparently healthy controls. Each subject underwent a hydrogen breath test using 10 g lactulose after an overnight fast. An SC Microlyser from Quintron, USA, was used to measure methane and hydrogen at baseline and at every 30 min for 4 h. Subjects with fasting methane concentration <10 p.p.m. were labeled as low methane producers (LMPs) and > 10 p.p.m. as predominant methane producers (PMPs). Results The IBS and control groups included 66.78% and 67.53% men, respectively. Mean age in the two groups was 48.52 ± 30.54 years (range 15–68 years) and 45.67 ± 30.54 years (range 15–78 years), respectively. Prevalence of predominant methanogenic flora in IBS and control groups was 14.5% (50/345) and 34.6% (88/254), respectively (P < 0.001). Fifty-two out of 254 (20.6 %) were PMPs and 36 out of 254 (14.0%) were LMPs in controls. In contrast to this, IBS patients had 17 out of 354 (4.9%) that were PMPs and 33 out of 345 (9.6%) that were LMPs. Conclusion Methanogenic flora was significantly lower in IBS patients from North India than in apparently healthy subjects. This may be one of the causes of flatulence in IBS patients.     

Effect of Predominant Methanogenic Flora on Outcome of Lactose Hydrogen Breath Test in Controls and Irritable Bowel Syndrome Patients of North India

The relationship between methanogenic flora and hydrogen (H₂) production is considered to be a possible confounding factor in the interpretation of hydrogen breath tests (H₂BT). Therefore, the present study was conducted prospectively and included 154 IBS patients (fulfilling Rome II criteria) and 286 age-and-sex-matched apparently healthy controls. Each subject underwent H₂BT after overnight fasting using 25 g lactose. Methane and H₂ were measured using an SC Microlyser from Quintron, USA, at baseline and every 30 min for a total of 4 h. Subjects with fasting methane concentration <10 ppm were labeled as low methane producers (LMP) and >10 ppm as predominant methane producers (PMP). A rise >20 ppm over base line in hydrogen concentration was taken as +ve hydrogen breath test. IBS and control groups included 66.78% and 67.53% males, respectively. Mean age in the two groups were 48.52 ± 30.54 years (range 15–68 years) and 45.67 ± 30.54 years (range 15–78 years), respectively. Hydrogen breath test was +ve in 77/154 (50%) IBS patients and in 142/286 (49.65%) in controls (P > 0.05). It was also observed that the hydrogen breath test was −ve due to PMP in 5/77 (6.49%) of IBS patients and in 29/154 (20.14%) in controls. PMP affected lactose hydrogen breath tests in 6.49–20.14% subjects. This effect is more apparent in apparently healthy subjects as compared to patients with IBS.     

Alterations of the colonic flora and their effect on the hydrogen breath test

The hydrogen breath test was performed by ingestion of 20 g lactulose and analysis of end-expiratory air. Eighteen patients undergoing colonoscopy, 17 receiving antibiotics, 12 prepared for colon surgery, and 15 controls were examined. The test was repeated under control conditions in the treated patients. Eleven of 55 subjects failed to produce significant amounts of hydrogen under control conditions. This 20% proportion of non-hydrogen producers is much higher than that reported by other investigators. The hydrogen production was very markedly depressed after preparation for colonscopy and antibiotic therapy. The effect of neomycin and enemata as used in preparation for colon surgery was less marked. Hydrogen production by the colonic flora is thus subject to individual variations and may be affected by various therapeutic regimens. All these may cause false negative results when using the hydrogen breath test to evaluate carbohydrate absorption. The test should therefore not be performed for a considerable time after therapeutic manipulation of the colonic flora.     

Starch malabsorption and breath gas excretion in healthy humans consuming low- and high-starch diets

Dietary starch delivery to the colon and excretion in stools and the ability of unabsorbed carbohydrates to promote hydrogen and methane release in breath were evaluated in 6 volunteers during two 8-day periods on starch diets of 100 and 300 g, respectively. Significantly less starch was recovered from the terminal ileum by aspiration per 24 h during the low-starch period (4.1 +/- 0.3 vs. 9.5 +/- 1.1 g, mean +/- SEM, p less than 0.01). Unabsorbed glucose tended to rise during the high-starch period (2.7 +/- 0.8 vs. 1.1 +/- 0.3 g). Fecal outputs of starch, glucose, volatile fatty acids, and lactic acid were not significantly different during the two periods. Daily breath hydrogen excretion was unchanged (181.2 +/- 22.7 vs. 193.7 +/- 19.8 ml for the low- and high-starch periods, respectively), whereas breath methane excretion increased markedly in the three methane producers during the high-starch period (217.2 +/- 80.9 vs. 32.4 +/- 7.3 ml). Starch malabsorption in the healthy small intestine was moderate even with a high-starch diet and less than that previously estimated by indirect methods. Unabsorbed starch catabolism by the colonic flora does not seem to explain most of the breath hydrogen excretion.     

Lack of effect of lactose digestion status on baseline fecal microflora

BACKGROUND:

The genetics of intestinal lactase divide the world’s population into two phenotypes: the ability (a dominant trait) or inability (a recessive trait) to digest lactose. A prebiotic effect of lactose may impact the colonic flora of these phenotypes differently.

OBJECTIVE:

To detect and evaluate the effects of lactose on subjects divided according to their ability to digest lactose.

METHODS:

A total of 57 healthy maldigesters (n=30) and digesters (n=27) completed diet questionnaires, genetic and breath hydrogen testing, and quantitative stool analysis for species of bacteria. Log₁₀ transformation of bacterial counts was compared with lactose intake in both groups using multiple regression analysis.

RESULTS:

There was a significant relationship between genetic and breath hydrogen tests. Daily lactose intake was marginally lower in lactose maldigesters (median [interquartile range] 12.2 g [31 g] versus 15 g [29.6 g], respectively). There was no relationship between lactose intake and breath hydrogen tests in either group. There were no differences in bacterial counts between the two groups, nor was there a relationship between bacterial counts and lactose intake in either group.

CONCLUSION:

The differential bacterial effects of lactose were not quantitatively detected in stool samples taken in the present study.     

Respiratory methane excretion in children with lactose intolerance

Two evaluate the relationship between colonic methane production and carbohydrate malabsorption, we measured end-expiratory methane levels in 70 normal and 40 lactose-intolerant children. Time-dependent excretion of hydrogen and methane was determined every 30 min for 120 min following a fasting oral lactose challenge (2 g/kg). Mean breath hydrogen levels in normals (lactose-tolerant) equaled 3.7 parts per million (ppm) throughout the study, but increased to >10 ppm by 60 min and remained elevated in lactose-intolerant subjects. Breath methane in normal children averaged 1.6 ppm from 0 to 120 min. In contrast, CH₄ excretion by lactose-intolerant children averaged 5.1 ppm at 90 min; and, by 120 min levels increased significantly compared with control. Breath methane levels in lactose-intolerant subjects following a lactose load continued to increase, however, despite the coingestion of exogenous lactase in amounts calculated to result in complete hydrolysis of the disaccharide. These data demonstrate that lactase-deficient children manifest significant increases in breath methane excretion following lactose ingestion and that enhanced methane production may be a consequence of several factors, including altered fecal pH and increased methanogenic substrates provided by colonic lactose fermentation. Further studies are required to determine the clinical significance of elevated methane production in lactose intolerance.     

Effect of Dietary Turmeric on Breath Hydrogen

Turmeric is widely used in Indian cuisine. The main constituents of turmeric are curcumin and its analogues, which are well-known antioxidant compounds. In the present study, we hypothesized that turmeric in curry might increase bowel motility and activate hydrogen-producing bacterial flora in the colon, thereby increasing the concentration of breath hydrogen. Eight healthy subjects fasted for 12 h and ingested curry and rice with or without turmeric (turmeric knockout curry). Breath-hydrogen concentrations were analyzed every 15 min for 6 h by gas chromatography with a semiconductor detector. Curry with turmeric significantly increased the area under the curve of breath hydrogen and shortened small-bowel transit time, compared with curry not containing turmeric. These results suggested that dietary turmeric activated bowel motility and carbohydrate colonic fermentation.     

Lactase deficiency and lactose intolerance-related symptoms in adult healthy subjects from western France]

The prevalence of lactase deficiency (LD) and lactose intolerance is not well known in France. Using breath hydrogen and methane analysis after 50 g oral lactose load, we investigated the prevalences of LD, lactose intolerance, and methane producer status in 102 healthy adults born in western France, and we examined the relationships between these parameters and the daily milk consumption. In 10 subjects with LD and lactose intolerance, we studied the reproducibility of the lactose hydrogen breath test results for the diagnosis of LD and lactose intolerance and estimated the quantity of lactose malabsorbed in comparison with the lactulose hydrogen breath test. The prevalence of LD was 23.4 percent and symptoms of lactose intolerance were observed in 50 percent of the 24 subjects with LD. The daily milk consumption was not significantly different in the 24 subjects with LD and in the 78 subjects without LD (281 +/- 197 vs 303 +/- 217 ml/24 h). The prevalence of methane producer status was 42.1 percent. The symptomatic group of lactose malabsorbers (n = 12) was characterized by a shorter lactose mouth to caecum transit time (39 +/- 20 vs 88 +/- 48 min; P less than 0.05), and more marked hydrogen production (6.1 +/- 2.3 vs 3.4 +/- 2.4 10(3) ppm.min; P less than 0.04). In the 10 subjects with LD and lactose intolerance, the hydrogen breath test was reproducible for diagnosis of LD and lactose intolerance, and for hydrogen production. The quantity of lactose malabsorbed was 60 percent. In France, symptoms of lactose intolerance are not severe and do not affect the daily consumption of milk and dairy products.     

Intestinal and Gastric Bypass

Jejunal bacterial flora, bile acid deconjugation, and breath hydrogen and methane excretion were studied in nine patients with end-to-side and nine patients with end-to-end jejunoileostomy and in eight patients with gastric bypass. Bacterial numbers did not differ significantly between healthy controls and any of the patient groups. Production of fermentation gases in anaerobic cultures supplemented with carbohydrates did not occur with jejunal secretions from healthy controls but was found in all intestinal bypass patients and half the gastric bypass patients. Bacterial bile acid deconjugation activity was significantly higher in end-to-side compared with end-to-end jejunoileostomy patients. In gastric bypass patients bile acid deconjugation was not significantly affected. Breath hydrogen after glucose ingestion was abnormal in six patients with end-to-side and three with end-to-end jejunoileostomy and in six of the patients subjected to gastric bypass. The highest values were found in the latter group. Breath methane, which is found in one third of a healthy population, was absent in all 18 patients with intestinal bypass, and this may indicate that a change occurs even in the colonic microflora after this operation. Both intestinal and gastric bypass may change the small-bowel microflora, with the greatest changes occurring after end-to-side jejunoileostomy and the least changes after gastric bypass.     

Influence of a Methanogenic Flora on the Breath H2 and Symptom Response to Ingestion of Sorbitol or Oat Fiber

Background and Objectives: We investigated the possibility that a variant of the normal colonic flora, a high concentration of methanogeas, influences the host's response to ingestion of nonabsorbable, fermentable materials. Methods: To better evaluate symptomatic and breath H₂ and methane (CH₄) responses, subjects were placed on a basal diet (primarily rice and hamburger) that contained minimal amounts of nonabsorbable, fermentable substrate. A breath CH₄/H₂ ratio of greater or less than 1 on the second day of the basal diet was used to categorize subjects as high (N = 9) or low (N = 25) CH₄ producers. After stabilization of the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested either sorbitol (8.8 g) or oat fiber (10.2 g). Results: The low CH₄ producers had a signficantly higher ( p < 0.05) breath H₂ concentration than the high producers on the basal diet and after ingestion of sorbitol (27.1 ± 2.7 ppm vs 15.8 ± 3.6 ppm) or oat fiber (13.1 ± 0.08 ppm vs 9.6 ± 1.2 ppm). Low producers of methane reported significantly increased bloating and cramping after sorbitol ingestion and increased bloating after fiber ingestion, whereas high CH₄ producers reported no signficant increase in these symptoms. Conclusion: The presence of a methanogenic flora is associated with a reduced symptomatic response to ingestion of nonabsorbable, fermentable material in healthy subjects. Manipulation of the normal flora could be of therapeutic value in nonmethanogenic patients with irritable bowel syndrome.     

Usefulness of the double-balloon enteroscope in colonoscopies performed in patients with previously failed colonoscopy

Jejunal flora, bile acid deconjugation, and breath hydrogen (H₂) and methane (CH₄) excretion were studied in 22 Billroth II (BII)-operated patients with chronic postprandial symptoms, dumping (9), vomiting (7), pain (10), and diarrhoea (14). Sixteen were below 90% of desirable weight. Two control groups were included, one comprising 5 symptom-free, BII-operated volunteers and another comprising 12 healthy, unoperated volunteers. The numbers of bacteria recovered from jejunal secretions in the postgastrectomy patients did not differ significantly from those recovered in the symptom-free BII-operated controls but were significantly lower in the unoperated controls. Production of fermentation gas in anaerobic media supplemented with carbohydrates occurred in 17 of 22 postgastrectomy patients and in 4 of 5 BII-operated controls but in none of the unoperated controls. Bacterial bile acid decon-jugating activity did not differ significantly between the postgastrectomy patients and the BII-operated controls but was significantly lower in the unoperated controls. Breath H₂ excretion after glucose ingestion was significantly higher in the postgastrectomy patients than in both the BII-operated and the unoperated controls. The addition of pectin or guar gum to the glucose meal largely prevented postprandial symptoms and breath hydrogen excretion. Six out of 12 postgastrectomy patients treated with metronidazole recorded symptomatic effects, mainly on diarrhoea. Our findings indicate that jejunal bacterial overgrowth may be a major cause of the symptoms in some postgastrectomy patients. The tests available for demonstration of small-bowel bacterial overgrowth, perhaps with the exception of the glucose H₂ breath test, did not differentiate satisfactorily between symptom-producing and non-symptom-producing abnormal jejunal flora. Thus these tests may seem to have a limited practical diagnostic value in such patients.     

Methane excretion in man--a study of breath, flatus, and faeces.

In this paper aspects of the variability of methane producing status have been examined, and a survey of breath methane excretion in various clinical and control populations is reported. Prevalences of methane excretion were 54% in healthy controls, 53% in non-gastrointestinal patients and 32% in gastrointestinal patients. Patients with Crohn's disease, ulcerative colitis, and pneumatosis cystoides intestinalis had significantly lower prevalences of methane excretion (13%, 15%, and 11% respectively). Faecal constituents and in vitro incubation analysis were similar in breath methane excretors and non-excretors. Several patients did not excrete methane in the breath although methane was present in colonic gas. The results indicate that different gastrointestinal patient groups have different prevalences of breath methane excretion and that all healthy subjects may produce methane but only when the production reaches a threshold does it appear in the breath.     

Feeding and colonic distension provoke altered autonomic responses in irritable bowel syndrome

OBJECTIVE: Alterations in autonomic balance, detectable by heart rate variability (HRV) analysis, have been shown to occur after a meal in patients with irritable bowel syndrome (IBS). There are few data on changes in sympathovagal responses in IBS to other forms of enteric stimulation such as colonic distension. The aim of this study was to determine the effects of colonic balloon distension on HRV in the fasting and the postprandial state in healthy subjects and in IBS patients. MATERIAL AND METHODS: Eight IBS patients and 8 age- and gender-matched healthy subjects underwent unsedated descending colonic distension before and after a 1000 kcal liquid meal. Low- (LF) and high-frequency (HF) HRV band values obtained from 2-min ECG segments recorded before and during distension were compared between groups, and between fasting and postprandial states. A visual analogue scale was used to determine sensation during colonic distension. RESULTS: HF values decreased significantly with feeding in IBS patients (p=0.01), but not in healthy subjects. The low-to-high frequency (LF/HF) ratio was significantly higher postprandially in IBS patients (p=0.02) and, additionally, was decreased (p<0.01) with colonic distension in the fed state, independently of colonic sensitivity or distending volume. Moreover, changes in the LF/HF ratio with distension in the fed versus the fasting state were negatively correlated in IBS patients but positively correlated in healthy subjects (both p<0.05). CONCLUSIONS: IBS patients demonstrated altered autonomic responses to feeding and colonic distension. Further studies should determine whether these alterations could explain the postprandial exacerbation of symptoms in IBS.     

Fecal skatole and indole and breath methane and hydrogen in patients with large bowel polyps or cancer

Summary The object of this study was to explore the use of fecal skatole and indole and breath methane and hydrogen as metabolic markers of the anaerobic colonic flora in patients with unresected large bowel cancer or polyps. Patients with descending or sigmoid colon cancer were more likely to be breath methane excretors than control subjects, patients with proximal colon cancer, and patients with rectal cancer. Control subjects excreting breath methane excreted less fecal skatole than breath methane excretors in the following groups: patients with adenomatous polyps, all patients with colorectal cancer, patients with proximal colon cancer, patients with descending and sigmoid colon cancer, and patients with rectal cancer. These data suggest that fecal skatole excretion equal to or greater than 100 g/g feces might be useful to discriminate colorectal cancer patients from control subjects. Twenty-nine percent (8 of 28) of the cancer patients had both high skatole levels and breath methane excretion compared with only 2% (1 of 41) of the control subjects (P<0.01).Supported by Public Health Service Grant CA-29056 from the National Cancer Institute     

Alternative pathways for hydrogen disposal during fermentation in the human colon.

Hydrogen gas, which is produced during fermentation in the human colon, is either excreted in breath or metabolised by gut bacteria through a variety of pathways. These may include methanogenesis, dissimilatory sulphate reduction, and acetogenesis. To determine which of these routes predominates in the large intestine, stools were taken from 30 healthy subjects and incubated as 5% (w/v) slurries with Lintner's starch. In 23 of 30 subjects, methane production was the main method of hydrogen disposal. In the remaining seven, high rates of sulphate reduction were recorded together with raised production of H2S. All samples showed relatively low rates of hydrogen evolution and of acetate formation from CO2 and H2. Sulphate reduction and methanogenesis seem to be mutually exclusive in the colon and this is probably linked to sulphate availability. Sulphate reduction, methanogenesis, and acetogenesis were strongly influenced by pH. Sulphate reduction was optimal at alkaline pH values whereas methane production was maximal at a neutral pH and acetogenesis favoured acidic conditions. Faecal H2S values were related to carriage of sulphate reducing bacteria. These data show that a number of competing pathways for hydrogen disposal are possible in the large gut and that a variety of factors such as colonic pH and sulphate availability can determine which of these mechanisms predominates.     

Effect of Guar, Pectin, Psyllium, Soy Polysaccharide, and Cellulose on Breath Hydrogen and Methane in Healthy Subjects

Different types of dietary fiber are fermented to various extents in vitro, but little is known about the effects of fiber on breath hydrogen and methane levels in vivo. Therefore, we studied the effects on breath hydrogen and methane of 15 g of guar, pectin, psyllium, soy polysaccharide, or cellulose in eight healthy subjects over a 12-h period. None of the fibers had a significant effect on breath hydrogen or methane concentrations, compared with the control (fasting). The four methane producers had lower breath hydrogen levels than the nonproducers 1 h after 15 g of lactulose (3 +/- 1 vs. 42 +/- 9, p less than 0.005) and 5-12 h after the different fibers (3.3 vs. 4.8 ppm; pooled SEM = 0.8; p less than 0.025). When the methane responses of the methane producers were expressed as increments relative to the control, there were small differences between treatments, with guar producing a larger response, 8.2 +/- 3.3 ppm, than cellulose, -2.9 +/- 2.3 ppm (p less than 0.05). The incremental methane responses of the different fibers in vivo were related to the previously reported production of propionic acid (r = 0.94, n = 5, p less than 0.02) and methane (r = 0.93, n = 4, NS) from in vitro fermentation of the same fibers. We conclude that methane producers have lower breath hydrogen levels than nonproducers. Purified fermentable and nonfermentable dietary fibers have no effect on breath hydrogen levels over 12 h in subjects previously consuming a normal diet. However, fermentable fibers may produce small increases in breath methane in methane-producing subjects.     

Methane and the Gastrointestinal Tract

Introduction

Several gases are produced through enteric fermentation in the intestinal tract. Carbon dioxide, hydrogen, hydrogen sulfide, and methane are thought to be the most common of these. Recent evidence suggests that methane may not be inert. In this review article, we summarize the findings with methane.

Methods

This is a review article discussing the various component gases in the gastrointestinal tract and their relevance to health and disease. Specific attention was paid to understanding methane.

Results

The majority of these gases are eliminated via flatus or absorbed into systemic circulation and expelled from the lungs. Excessive gas evacuation or retention causes gastrointestinal functional symptoms such as belching, flatulence, bloating, and pain. Between 30 and 62% of healthy subjects produce methane. Methane is produced exclusively through anaerobic fermentation of both endogenous and exogenous carbohydrates by enteric microflora in humans. Methane is not utilized by humans, and analysis of respiratory methane can serve as an indirect measure of methane production. Recent literature suggests that gases such as hydrogen sulfide and methane may have active effects on gut function. In the case of hydrogen sulfide, evidence demonstrates that this gaseous product may be produced by human eukaryotic cells. However, in the case of methane, there is increasing evidence that this gas has both physical and biological effects on gut function. It is now often associated with functional constipation and may have an active role here.

Conclusion

This review of the literature discusses the significance of enteric flora, the biogenesis of methane, and its clinical associations. Furthermore, we examine the evidence for an active role of methane in gastrointestinal motility and the potential applications to future therapeutics.     

Reliability and Reproducibility of Breath Hydrogen and Methane in Male Diabetic Subjects

We studied the variability and reliability ofbreath hydrogen and methane as well as the alterationsin intestinal gas profile in response to lactuloseingestion in 13 asymptomatic male patients with diabetes mellitus (DM). Seventeen healthy subjectsserved as controls. The prevalence of methane producerswas 33% in DM and 45% among control subjects (P NS). Theprevalence of nonhydrogen producers was 7.7% and 5.9%, respectively. The coefficient forinterday variation of H was 72.6 ± 9.8% in DM and49.7 ± 9.8% in controls (P < 0.05). 2Similarly, the coefficient for interday variation ofCH₄ was 94.3 ± 18.8 and 69.4 ±16.8% respectively (P = NS). The reproducibility ofbasal H₂ and CH₄ among diabeticsas assessed by r₁ (measure of reliability)was poorer among diabetics when breath analysis wasperformed on different days (P < 0.001). There was no significantdifference between diabetics and controls with respectto basal or peak or area under the curve forH₂ and CH₄ in response tolactulose. We conclude that there is poor reproducibility of fasting breath gas levelsamong asymptomatic male subjects with diabetes. Inaddition, DM is not associated with alterations inhydrogen- or methane-producing potential.