Fabrizis L. Suarez

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Colonic bacteria liberate large quantities of the highly toxic gases hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). The colonic mucosa presumably has an efficient means of detoxifying these compounds, which is thought to occur through methylation of H(2)S to CH(3)SH and CH(3)SH to dimethylsulfide (CH(3)SCH(3)). We investigated this detoxification pathway by incubating rat cecal mucosal homogenates with gas containing H(2)S, CH(3)SH, or CH(3)SCH(3). Neither CH(3)SH nor CH(3)SCH(3) was produced during H(2)S catabolism, whereas catabolism of CH(3)SH liberated H(2)S but not CH(3)SCH(3). Thus, H(2)S and CH(3)SH are not detoxified by methylation to CH(3)SCH(3). Rather, CH(3)SH is demethylated to H(2)S, and H(2)S is converted to nonvolatile metabolites. HPLC analysis of the homogenate showed the metabolite to be primarily thiosulfate. Analysis of cecal venous blood obtained after intracecal instillation of H(2)(35)S revealed that virtually all absorbed H(2)S had been oxidized to thiosulfate. The oxidation rate of H(2)S by colonic mucosa was 10,000 times greater than the reported methylation rate. Conversion to thiosulfate appears to be the mechanism whereby the cecal mucosa protects itself from the injurious effects of H(2)S and CH(3)SH, and defects in this detoxification possibly could play a role in colonic diseases such as ulcerative colitis.

Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour

Background/Aims—While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour. Methods—Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus output. The concentrations of sulphur-containing gases in each passage were correlated with odour intensity assessed by two judges. Odour intensity was also determined after treatment of flatus samples with zinc acetate, which binds sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal. Utilising gas-tight Mylar pantaloons, the ability of a charcoal lined cushion to adsorb sulphur-containing gases instilled at the anus of eight subjects was assessed. Results—The main sulphur-containing flatus component was hydrogen sulphide (1.06 (0.2) μmol/l), followed by methanethiol (0.21 (0.04) μmol/l) and dimethyl sulphide (0.08 (0.01) μmol/l) (means (SEM)). Malodour significantly correlated with hydrogen sulphide concentration (p⩽0.001). Zinc acetate reduced sulphur gas content but did not totally eliminate odour, while activated charcoal removed virtually all odour. The cushion adsorbed more than 90% of the sulphur gases. Conclusion—Sulphur-containing gases are the major, but not the only, malodorous components of human flatus. The charcoal lined cushion effectively limits the escape of these sulphur-containing gases into the environment.

Bismuth subsalicylate markedly decreases hydrogen sulfide release in the human colon

BACKGROUND & AIMS Hydrogen sulfide is one of the main malodorous compounds in human flatus. This toxic gas also has been implicated in the pathogenesis of ulcerative colitis. Therefore, a treatment that reduces colonic H2S levels could be clinically useful in the treatment of flatus odor and of ulcerative colitis. In this study the ability of bismuth subsalicylate, a compound that binds H2S, to reduce H2S release in the colon, was tested. METHODS Homogenates made from human and rat feces were incubated with and without bismuth subsalicylate, and gas production was measured. Fecal samples from 10 healthy subjects were analyzed before and after ingestion of bismuth subsalicylate (524 mg four times a day) for 3-7 days. RESULTS Fecal homogenates showed a dose-dependent relationship between the concentration of bismuth subsalicylate and H2S release. Treatment of subjects with bismuth subsalicylate produced a >95% reduction in fecal H2S release. CONCLUSIONS The ability of bismuth subsalicylate to dramatically reduce H2S could provide a clinically useful means of controlling fecal and/or flatus odor and of decreasing the putative injurious effects of H2S on the colonic mucosa.

Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal.

In a double-blind, crossover study, wedetermined whether microencapusulated pancreatic enzymesreduce postprandial symptoms experienced by healthyvolunteers after ingestion of a high calorie, high fat meal. At 7 AM, 18 subjects ingested 185 g ofcookies (1196 calories and 72 g of fat) with threepancrelipase capsules or a placebo. The severity ofgastrointestinal symptoms and flatus passages wererecorded for 15-17 hr, and end-alveolar samples wereobtained hourly for 10 hr. Ingestion of pancreaticsupplements was associated with a significant (P =0.049) reduction in bloating over the entire recordingperiod, and with significant reductions in bloating,gas, and fullness during the dinner to bedtime period.Pancreatic supplements had no significant effect onbreath H2 or CH4 concentration.The finding that pancreatic supplements reduce postprandial symptoms inhealthy subjects suggests that these supplements alsomight be beneficial in irritable bowelsyndrome.

Gas production by feces of infants.

Background Intestinal gas is thought to be the cause abdominal discomfort in infants. Little is known about the type and amount of gas produced by the infants colonic microflora and whether diet influences gas formation. Methods Fresh stool specimens were collected from 10 breast-fed infants, 5 infants fed a soy-based formula, and 3 infants fed a milk-based formula at approximately 1, 2, and 3 months of age. Feces were incubated anaerobically for 4 hours at 37°C followed by quantitation of hydrogen (H 2 ), methane (CH 4 ), carbon dioxide (CO 2 ), hydrogen sulfide (H 2 S), methanethiol (CH 3 SH), and dimethyl sulfide (CH 3 SCH 3 ) in the head-space. Results H 2 was produced in greater amounts by breast-fed infants than by infants in either formula group, presumably the consequence of incomplete absorption of breast milk oligosaccharides. CH 4 was produced in greater amounts by infants fed soy formula than by infants on other diets. CO 2 was produced in similar amounts by infants in all feeding groups. Production of CH 3 SH was conspicuously low by feces of breast-fed infants and production of H 2 S was high by soy-formula–fed infants. CH 3 SCH 3 was not detected. Only modest changes with age were observed and there was no relation between gas production and stool consistency, although stools were more likely to be malodorous when concentrations of H 2 S and/or CH 3 SH were high. Conclusions Gas release by infant feces is strongly influenced by an infants diet. Of particular interest are differences in production of the highly toxic sulfur gases, H 2 S and CH 3 SH, because of the role that these gases may play in certain intestinal disorders of infants.

Binding of hydrogen sulfide by bismuth does not prevent dextran sulfate-induced colitis in rats.

Several lines of evidence suggest that ulcerative colitis could be caused by excessive bacterial production of H2S in the colon. A rodent model of colitis involves the feeding of nonabsorbable, carbohydrate-bound sulfate in the form of dextran sulfate or carrageenan. The observation that metronidazole blocks the development of this colitis suggested that the injurious agent could be a sulfur-containing compound (such as H2S) that is released during the bacterial metabolism of the nonabsorbed sulfate. We tested this possibility by feeding rats dextran sulfate, with or without bismuth subsalicylate, a compound that avidly binds H2S. Bismuth subsalicylate reduced the fecal release of H2S in dextran sulfate-treated rats to values well below that of controls. Nevertheless, all the animals developed colitis. We conclude that excessive H2S production does not play a role in the dextran sulfate model of colitis.

Failure of activated charcoal to reduce the release of gases produced by the colonic flora

Objective: Activated charcoal is used to treat excessive volume or malodor of intestinal gas. Our previous studies demonstrated that activated charcoal failed to bind appreciable quantities of the volumetrically important gut gases. However, the odor of feces and flatus derives primarily from trace quantities of sulfur-containing gases, primarily H2S and methanethiol, which should avidly bind to activated charcoal. The goal of this study was to determine if ingestion of activated charcoal reduces the fecal release of sulfur gases. Methods: Five healthy human volunteers ingested 0.52 g of activated charcoal four times daily for 1 wk and the fecal liberation of intestinal gases was measured before and after the activated charcoal treatment. In an effort to explain the in vivo results, additional in vitro studies were performed to compare the binding capacity of charcoal to the sulfur gas released by feces. Results: Ingestion of activated charcoal produced no significant reduction in the fecal release of any of the sulfur-containing gases, nor was total fecal gas release or abdominal symptoms significantly influenced. In vitro studies suggested that the failure of ingested charcoal to reduce liberation of sulfur gases probably is explained by the saturation of charcoal binding sites during passage through the gut. Conclusion: Commonly employed doses of activated charcoal do not appreciably influence the liberation of fecal gases.

Evaluation of an extremely flatulent patient: Case report and proposed diagnostic and therapeutic approach

We recently encountered a patient with severe flatulence who previously had been subjected to innumerable diagnostic tests and ineffective therapies based on the belief that his rectal gas was produced in the colon. Analysis of three flatus samples demonstrated that nitrogen (N2) was the predominant flatus gas whereas the three gases produced in the gut (CO2, H2 [hydrogen], and CH4 [methane]) comprised <16% of rectal gas. This result plus a series of other diagnostic tests clearly indicated that the patients flatus was derived almost entirely from swallowed air. Based on this case, the present report summarizes available data on excessive flatulence and suggests a rational approach to the patient complaining of this problem. Particular emphasis is placed upon a sequential strategy consisting of: 1) a count of flatus passages to determine if the subject truly is abnormal (normal: <20 passages/day); 2) an analysis of flatus to determine if the flatus originates from swallowed air (predominantly nitrogen) or intraluminal production (predominantly CO2, H2, and CH4); and 3) treatment based upon the origin of the rectal gas.

Measurement of fecal sulfide using gas chromatography and a sulfur chemiluminescence detector

We describe a simple technique to measure sulfide in fecal homogenates (or any other liquid milieu), which involves acidification followed by the G.C. measurement of H2S in a gas space equilibrated with a small quantity of homogenate. An internal standard of Zn35S added to the homogenate permits correction for incomplete recovery of H2S in the gas space. The use of a sulfur chemiluminescence detector, which specifically and sensitively responds to sulfur-containing compounds, greatly facilitates this measurement.

Tolerance of formulas containing prebiotics in healthy, term infants.

Objective: The aim of the study was to compare infants’ gastrointestinal tolerance of formulas supplemented with 2 different levels of galacto-oligosaccharides (GOS) versus a control formula (CF) or human milk. Methods: Healthy, full-term infants (n = 180) were enrolled in this 3-group controlled, double-blind, multicenter study, and a concurrently enrolled, nonrandomized human milk–fed group (HM) by 8 days of age. Infants were randomized to be fed formula supplemented with either 4 g (EF4) or 8 g (EF8) GOS/L or a CF until day of life (DOL) 119. Infants were to be seen at DOL 14, 35, 56, 84, and 119. Parents were to record detailed 24-hour information about intake, tolerance to feedings, and stool patterns and consistency each day from enrollment to DOL 35, and for 3 days before DOL 56, 84, and 119. Stool consistency was scored on a 5-point scale as watery (1), loose/mushy, soft, formed, or hard (5). Results: The mean stool consistency score was higher in the CF group throughout the study (CF > EF8 and CF > HM for all study periods and CF > EF4 from DOL 15 to 35, P < 0.05). There was a significantly higher percentage of watery stools in the EF8 versus the CF group from study day 1 (SD 1) to DOL 14 (P < 0.05), but no differences between the groups in number of stools per day. The percentage of feedings with spit up and/or vomiting within 1 hour after feeding was significantly lower for HM versus EF8 and CF from SD 1 to DOL 14 (P < 0.05). Conclusions: In this clinical study, milk-based term infant formula (Similac Advance) with 4 g GOS/L was well-tolerated in terms of stool consistency and additional measures of gastrointestinal tolerance by newborn infants through the first 4 months of life.