Gastroenterology
Volume 123, Issue 3 , Pages 933-935, September 2002

Much to do about gas☆☆☆

Clinical Enteric Neuroscience Translational & Epidemiological Research Program (C.E.N.T.E.R.) Mayo Foundation Rochester, Minnesota

Article Outline

Abstract 

GASTROENTEROLOGY 2002;123:933-935

 

See article on page 700.

In this issue of GASTROENTEROLOGY, an article by the Barcelona group1 extends the observations on the relationship between intraluminal fat, transit of gas, and its relevance to the irritable bowel syndrome (IBS). The authors show that intestinal gas transit is delayed by intraduodenal infusion of lipids. The concentration of fat and caloric infusion rates are consistent with the prior literature showing the effects of lipids on gastric emptying, accommodation, and visceral perception. Serra et al. also show, as in previous studies in IBS patients,2 that patients with IBS and significant bloating have greater gas retention than healthy controls. They suggest that because IBS patients achieve high retention with abnormal perception at lower duodenal lipid loads compared with healthy controls, the patients might be hypersensitive to the effects of fat. These observations are consistent with the clinical experience of patients with bloating, who usually report that these symptoms are exacerbated by “rich” or high-fat content meals.

The study includes a large number of patients and controls, and uses a method to measure retention of gas and associated symptoms that has been shown to be reproducible and responsive to pharmacological modulation.2, 3 The IBS patients studied were in the predominantly constipated subgroup. A strength of the study was the use of intrarectal cannulas to collect evacuated gas, to avoid the potential confounder of an evacuation disorder in these patients. The observation of delayed gas transit is also consistent with slow small bowel and colonic transit of solid residue in constipated IBS patients.4

On the other hand, it is not clear that increased gas retention causes increased symptoms. For example, although lipid infusion of 0.5 Kcal/min increased gas retention compared with saline infusion in IBS patients, this was not accompanied by an increase in abdominal perception scores. It seems that in the presence of baseline visceral hypersensitivity to a stimulus (i.e., gas) in the IBS patients studied, an increased visceral afferent signal (gas plus intraduodenal lipid) does not lead to increased perception, but rather to altered motor responses such as reduced intestinal propulsion.

The authors propose the “gas-lipid challenge test” to positively diagnose IBS, based on the good discrimination between health and IBS patients with bloating. However, no data are provided regarding gas transit in patients with bloating and organic gastrointestinal diseases, and hence, the real validity of this test to differentiate functional from organic bowel syndromes requires further proof before this should be considered as a positive test for IBS.

Nevertheless, the experimental model is of interest, given the reproducibility of the results, responsiveness to pharmacological modulation,2 and the potential of the model to investigate interactions between different intraluminal stimuli (gas, dietary fats, or other nutrients) and the generation of symptoms and motor disturbances in functional gastrointestinal disorders.

Investigations conducted in animal models, healthy humans, and patients with functional diseases have explored the relationships between fat and the gut.5, 6, 7, 8, 9, 10, 11 This literature on integrative physiology over 5 decades (Table 1) provides the basis for novel approaches to deal with symptomatic effects of fat ingestion, which are discussed below.

Table 1. Review of effects of fat on gastrointestinal sensory and motor functions
The fat and caloric content of the meal influences the motor and myoelectrical response of the colon.5
Intraluminal fat heightens visceral perception and alter visceral motor reflexes.6
Fat is the most potent secretagogue of CCK.
Long chain fatty acids and chylomicrons formed during digestion of fat release CCK that activate vagal afferents through CCK-A receptors.7, 8, 9 This mechanism results in modulation of perception of gastric distention and reflex gut functions such as relaxation of the stomach5; the role of CCK on fat-induced retardation of gas transit through the gut requires further study.
Long chain fatty avids are more effective in releasing CCK than shorter chain fatty acids (<C12 chain length).10 Short chain fatty acids, such as butyrate, activate vagal afferents directly rather than via CCK.8
The length and location of the intestinal segment exposed to the fat determines the magnitude of its physiological effects.11

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What are the practical implications of these observations? 

Several strategies may facilitate the greater tolerance of dietary fats, which is a significant proportion of the modern diet in Western countries. Because the colonic response to feeding was more prominent with meals of >500 kcal, a first option would be to reduce the total calorie (and typically the fat) content of a meal. The rate of delivery of fat-calories to the duodenum influences symptoms in IBS (0.5 kcal/min)1 or functional dyspepsia (1–2 kcal/min).9 A second strategy would be to reduce the fat content, especially in the liquid phase of the diet, because this is likely to empty more rapidly. J. N. Hunt had shown almost 50 years ago that the stomach was capable of emptying nutrient liquids at a rate of 2 kcal/min.12 Restriction of fat is even more important in the presence of fat malabsorption because the hydrolyzable fat in the ileum results in the “ileal break”—inhibition of acid secretion, gastric emptying, and duodenojejunal motility.13 Because the stomach cannot reduce the delivery rate, changes in dietary fat composition should be considered.

Tetrahydrolipostatin (orlistat), a drug approved for treatment of obesity, inhibits the intraluminal breakdown of dietary fat preventing vagal activation and diminishing perception of gastric distention.14 Prevention of dietary fat hydrolysis by orlistat may reduce dyspeptic symptoms in response to fat ingestion. However, it may aggravate lower abdominal symptoms (possibly steatorrhea, gas) and formal studies are needed.

Dietary fat can be, at least partly, replaced with sucrose polyester to keep the rate of delivery of hydrolyzable fat to the duodenum below 0.5 kcal/min, which is the threshold level to induce gas transit effects in IBS. Sucrose polyesters have the physical properties and taste of fat but they do not activate cholecystokinin (CCK) release or stimulate vagal afferents.14 The degree of intestino-colonic motor disturbances with the sucrose polyester, olestra, is modest.15

Another strategy is to use CCK-A receptor antagonists (e.g., dexloxiglumide) to block fat-induced nociception and the altered motor reflex responses of the gut associated with the release of CCK in response to ingested nutrients, as observed in dyspepsia.14 A greater understanding of the effects of CCK and CCK-A and -B receptor antagonists on gastric emptying and accommodation, intestinal transit, and gastric and colonic sensation will facilitate application of these principles in treatment of patients with food-related symptoms.

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What other transmitters may be involved in fat-induced alterations of gut functions? 

Other potentially important transmitters/hormones mediating fat-induced intestinal disturbances are enteroglucagon, neurotensin and peptide YY,13, 16 and the ubiquitous gut transmitter serotonin.17 A neurotensin antagonist is presently being evaluated in clinical trials of patients with IBS. Immunoneutralization of peptide YY did not inhibit fat-induced reflexes in rats.18 The 5-HT3 antagonist, alosetron (Lotronex; Glaxo Wellcome), relieved dyspepsia in a large phase IIb trial19; pharmacodynamic studies suggest that the benefit results from reduced sensation of nausea or bloating,20, 21 not from a change in gastric compliance or volume of accommodation in the postprandial period.20, 21

Other hormones/transmitters including orexins,22 amylin, and GLP-1 and -2 may influence vagal afferent function,23 and their effects on reflex responses to dietary fats and nutrients need to be evaluated.

In summary, we hope the Barcelona group will understand if we defer the use of the “gas challenge test” for diagnosis of IBS until further clinical validation. However, their experimental model has potential to explore dietary and pharmacological approaches to resolve problems of gas and fat intolerance in patients. For integrative physiologists and clinical pharmacologists, there is still much to do about gas and fat in the bowel!

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References 

  1. Serra J, Salvioli B, Azpiroz F, Malagelada JR. Lipid-induced intestinal gas retention in the irritable bowel syndrome. Gastroenterology. 2002;123:700–706
  2. Caldarella MP, Serra J, Azpiroz F, Malagelada JR. Prokinetic effects in patients with intestinal gas retention. Gastroenterology. 2002;122:1748–1755
  3. Serra J, Azpiroz F, Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut. 2001;48:14–19
  4. Cann PA, Read NW, Brown C, Hobson N, Holdsworth CD. Irritable bowel syndrome: relationship of disorders in the transit of a single solid meal to symptom patterns. Gut. 1983;24:405–411
  5. Snape WJ, Matarazzo SA, Cohen S. Effect of eating and gastrointestinal hormones on human colonic myoelectrical and motor activity. Gastroenterology. 1978;75:373–378
  6. Feinle C, Grundy D, Read NW. Effects of duodenal nutrients on sensory and motor responses of the human stomach to distension. Am J Physiol. 1997;273:G721–G726
  7. Raybould HE, Meyer JH, Tabrizi Y, Liddle RA, Tso P. Inhibition of gastric emptying in response to intestinal lipid is dependent on chylomicron formation. Am J Physiol. 1998;274:R1834–R1838
  8. Lal S, Kirkup AJ, Brunsden AM, Thompson DG, Grundy D. Vagal afferent responses to fatty acids of different chain length in the rat. Am J Physiol Gastrointest Liver Physiol. 2001;281:G907–G915
  9. Feinle C, Meier O, Otto B, D'Amato M, Fried M. Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia. Gut. 2001;48:347–355
  10. McLaughlin J, Grazia Luca M, Jones MN, D'Amato M, Dockray GJ, Thompson DG. Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility. Gastroenterology. 1999;116:46–53
  11. Meyer JH, Tabrizi Y, DiMaso N, Hlinka M, Raybould HE. Length of intestinal contact on nutrient-driven satiety. Am J Physiol. 1998;275:R1308–R1319
  12. Hunt JN, Spurrell WR. The pattern of emptying of the human stomach. J Physiol. 1951;113:157–168
  13. Spiller RC, Trotman IF, Adrian TE, Bloom SR, Misiewicz JJ, Silk DB. Further characterisation of the “ileal brake” reflex in man—effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY. Gut. 1988;29:1042–1051
  14. Feinle C, Rades T, Otto B, Fried M. Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans. Gastroenterology. 2001;120:1100–1107
  15. Aggarwal AM, Camilleri M, Phillips SF, Schlagheck TG, Brown ML, Thomforde GM. Olestra, a nondigestible, nonabsorbable fat. Effects on gastrointestinal and colonic transit. Dig Dis Sci. 1993;38:1009–1014
  16. Feinle C, Grundy D, Otto B, Fried M. Relationship between increasing duodenal lipid doses, gastric perception, and plasma hormone levels in humans. Am J Physiol Regul Integr Comp Physiol. 2000;278:R1217–R1223
  17. Kirkup AJ, Brunsden AM, Grundy D. Receptors and transmission in the brain-gut axis: potential for novel therapies. I. Receptors on visceral afferents. Am J Physiol Gastrointest Liver Physiol. 2001;280:G787–G794
  18. Raybould HE, Tabrizi Y, Meyer JH, Walsh JH. PYY immunoneutralization does not alter lipid-induced inhibition of gastric emptying in rats. Regul Pept. 1999;79:125–130
  19. Talley NJ, Van Zanten SV, Saez LR, Dukes G, Perschy T, Heath M, et al. A dose-ranging, placebo-controlled, randomized trial of alosetron in patients with functional dyspepsia. Aliment Pharmacol Ther. 2001;15:525–537
  20. Kuo B, Camilleri M, Burton D, Viramontes B, McKinzie S, Thomforde G, et al. Effects of 5-HT(3) antagonism on postprandial gastric volume and symptoms in humans. Aliment Pharmacol Ther. 2002;16:225–233
  21. Zerbib F, Bruley des Varannes S, Oriola RC, McDonald J, Isal JP, Galmiche JP. Alosetron does not affect the visceral perception of gastric distension in healthy subjects. Aliment Pharmacol Ther. 1994;8:403–407
  22. Kirchgessner AL. Orexins in the brain-gut axis. Endocr Rev. 2002;23:1–15
  23. Delgado-Aros S, Kim DY, Burton DD, Thomforde GM, Stephens D, Brinkmann BH, et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol Gastrointest Liver Physiol. 2002;282:G424–G431

☆ Address requests for reprints to: Michael Camilleri, M.D., Mayo Clinic, Charlton 7-154, 200 First Street S.W., Rochester, Minnesota 55905. e-mail: camilleri.michael@mayo.edu.

☆☆ Supported by grants #R01-DK54681 and #K24-DK02638 from the National Institutes of Health (to M.C.). Dr. Camilleri has received research grants from Glaxo Wellcome, the manufacturer of Alosetron.

PII: S0016-5085(02)00181-6

Refers to article:

  • Lipid-induced intestinal gas retention in irritable bowel syndrome

    Jordi Serra, Beatrice Salvioli, Fernando Azpiroz, Juan–R. Malagelada
    Gastroenterology September 2002 (Vol. 123, Issue 3, Pages 700-706)

Gastroenterology
Volume 123, Issue 3 , Pages 933-935, September 2002

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