Duodenal implications in the pathophysiology of functional dyspepsia

Kwang Jae Lee, Jan Tack, Kwang Jae Lee, Jan Tack

Abstract

Functional dyspepsia (FD) is a heterogeneous disorder associated with diverse pathophysiologic mechanisms. Studies have shown duodenal implications in the pathophysiology of FD. Duodenal hypersensitivity to acid, increased duodenal acid exposure, and abnormal responses to duodenal lipids or released cholecystokinin have been observed in patients with FD. Moreover, there is evidence indicating duodenal immune activation in FD. Alterations in the number of duodenal eosinophils or intraepithelial lymphocytes have been reported in a subset of FD patients, particularly in patients with post-infectious FD. Whether these abnormalities in the duodenum play a crucial role in the generation of dyspeptic symptoms needs to be elucidated. Further investigations on the relationship between duodenal abnormalities and well-known pathophysiologic mechanisms of FD are required. Furthermore, the causative factors related to the development of duodenal abnormalities in FD warrant further study.

Keywords: Acids; Duodenum; Dyspepsia; Eosinophilia.

Conflict of interest statement

Conflicts of interest: None.

Figures

Figure 1
Figure 1
Duodenal implications in the pathophysiology of functional dyspepsia. CCK, cholecystokinin.

References

    1. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466–1479.
    1. Stanghellini V, Tosetti C, Paternico A, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology. 1996;110:1036–1042.
    1. Sarnelli G, Caenepeel P, Geypens B, Janssens J, Tack J. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98:783–788.
    1. Tack J, Piessevaux H, Coulie B, Caenepeel P, Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology. 1998;115:1346–1352.
    1. Tack J, Caenepeel P, Fischler B, Piessevaux H, Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 2001;121:526–535.
    1. Haug TT, Svebak S, Wilhelmsen I, et al. Psychological factors and somatic symptoms in functional dyspepsia. A comparison with duodenal ulcer and healthy controls. J Psychosom Res. 1994;38:281–291.
    1. Samsom M, Verhagen MA, vanBerge Henegouwen GP, Smout AJ. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology. 1999;116:515–520.
    1. Lee KJ, Demarchi B, Demedts I, Sifrim D, Raeymaekers P, Tack J. A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea. Am J Gastroenterol. 2004;99:1765–1773.
    1. Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in patients with functional dyspepsia and controls using a radiotelemetry pH monitoring system. J Clin Gastroenterol. 2009;43:527–533.
    1. Fried M, Feinle C. The role of fat and cholecystokinin in functional dyspepsia. Gut. 2002;51(suppl 1):i54–i57.
    1. Björnsson E, Sjöberg J, Ringström G, Norström M, Simrén M, Abrahamsson H. Effects of duodenal lipids on gastric sensitivity and relaxation in patients with ulcer-like and dysmotility-like dyspepsia. Digestion. 2003;67:209–217.
    1. Talley NJ, Walker MM, Aro P, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol Hepatol. 2007;5:1175–1183.
    1. Kindt S, Tertychnyy A, de Hertogh G, Geboes K, Tack J. Intestinal immune activation in presumed post-infectious functional dyspepsia. Neurogastroenterol Motil. 2009;21:832–e856.
    1. Collen MJ, Loebenberg MJ. Basal gastric acid secretion in nonulcer dyspepsia with or without duodenitis. Dig Dis Sci. 1989;34:246–250.
    1. George AA, Tsuchiyose M, Dooley CP. Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Gastroenterology. 1991;101:3–6.
    1. Talley NJ, Meineche-Schmidt V, Pare P, et al. Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies) Aliment Pharmacol Ther. 1998;12:1055–1065.
    1. di Stefano M, Vos R, Vanuytsel T, Janssens J, Tack J. Prolonged duodenal acid perfusion and dyspeptic symptom occurrence in healthy volunteers. Neurogastroenterol Motil. 2009;21:712–e740.
    1. Lee KJ, Kim JH, Cho SW. Dyspeptic symptoms associated with hypersensitivity to gastric distension induced by duodenal acidification. J Gastroenterol Hepatol. 2006;21:515–520.
    1. Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in patients with functional dyspepsia and controls using a radiotelemetry pH monitoring system. J Clin Gastroenterol. 2009;43:527–533.
    1. Akiba Y, Kaunitz JD. Luminal chemosensing and upper gastrointestinal mucosal defenses. Am J Clin Nutr. 2009;90:826S–831S.
    1. Mayer EA. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology. 1994;107:271–293.
    1. Lee KJ, Vos R, Janssens J, Tack J. Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans. Am J Physiol. 2004;286:G278–G284.
    1. Schwarz MP, Samsom M, Smout AJPM. Chemospecific alterations in duodenal perception and motor response in functional dyspepsia. Am J Gastroenterol. 2001;96:2596–2602.
    1. Houghton LA, Kerrigan DD, Read NW. Effect of intraduodenal infusion of acid on the antropyloroduodenal motor unit in human volunteers. J Gastrointest Motil. 1990;2:202–208.
    1. Hunt JN, Knox MT. The slowing of gastric emptying by four strong acids and three weak acids. J Physiol. 1972;222:187–208.
    1. Lin HC, Doty JE, Reedy TJ, et al. Inhibition of gastric emptying by acids depends on pH, titratable acidity, and length of intestine exposed to acid. Am J Physiol. 1990;259:G1025–G1030.
    1. Woodtli W, Owyang C. Duodenal pH governs interdigestive motility in humans. Am J Physiol. 1995;268:G146–G152.
    1. Lemon M, Dedering JP, Flourie B, et al. Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. Dig Dis Sci. 1991;36:1249–1254.
    1. Barbera R, Feinle C, Read NW. Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia. Eur J Gastroenterol Hepatol. 1995;7:1051–1057.
    1. 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.
    1. Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci. 1995;40:1636–1641.
    1. Barbera R, Peracchi M, Brighenti F, Cesana B, Bianchi PA, Basilisco G. Sensations induced by medium and long chain triglycerides: role of gastric tone and hormones. Gut. 2000;46:32–36.
    1. 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.
    1. Chua AS, Keeling PW, Dinan TG. Role of cholecystokinin and central serotonergic receptors in functional dyspepsia. World J Gastroenterol. 2006;12:1329–1335.
    1. Tack J, Depoortere I, Bisschops R, Verbeke K, Janssens J, Peeters T. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther. 2005;22:847–853.
    1. Tack J, Depoortere I, Bisschops R, et al. Influence of ghrelin on interdigestive gastrointestinal motility in man. Gut. 2006;55:327–333.
    1. Binn M, Albert C, Gougeon A, et al. Ghrelin gastrokinetic action in patients with neurogenic gastroparesis. Peptides. 2006;27:1603–1606.
    1. Murray CD, Martin NM, Patterson M, et al. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo-controlled crossover study. Gut. 2005;54:1693–1698.
    1. Cummings DE, Frayo RS, Marmonier C, Aubert R, Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol. 2004;287:E297–E304.
    1. Lee KJ, Cha DY, Cheon SJ, Yeo M, Cho SW. Plasma ghrelin levels and their relationship with gastric emptying in patients with dysmotility-like functional dyspepsia. Digestion. 2009;80:58–63.
    1. Piliponsky AM, Pickholtz D, Gleich GJ, Levi-Schaffer F. Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: a possible role for mast cells in late-phase allergic reactions. J Allergy Clin Immunol. 2001;107:993–1000.
    1. Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.
    1. Lee KJ, Kim YB, Kim JH, Kwon HC, Kim DK, Cho SW. The alteration of enterochromaffin cell, mast cell, and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors. J Gastroenterol Hepatol. 2008;23:1689–1694.
    1. Guilarte M, Santos J, de Torres I, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56:203–209.
    1. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147–174.
    1. Barbara G, Wang B, Stanghellini V, et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007;132:26–37.
    1. Powell N, Walker MM, Talley NJ. Gastrointestinal eosinophils in health, disease and functional disorders. Nat Rev Gastroenterol Hepatol. 2010;7:146–156.
    1. Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765–773.
    1. Martin ST, Collins CG, Fitzgibbon J, Lee G, Quigley EM, O'Sullivan GC. Gastric motor dysfunction: is eosinophilic mural gastritis a causative factor. Eur J Gastroenterol Hepatol. 2005;17:983–986.
    1. Murch S. Allergy and intestinal dysmotility-evidence of genuine causal linkage? Curr Opin Gastroenterol. 2006;22:664–668.
    1. Hogan SP, Mishra A, Brandt EB, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001;2:353–360.
    1. Mearin F, Pérez-Oliveras M, Perelló A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one-year follow-up cohort study. Gastroenterology. 2005;129:98–104.
    1. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology. 2002;122:1738–1747.
    1. Gargala G, Lecleire S, François A. Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia. World J Gastroenterol. 2007;13:2333–2338.
    1. Suzuki H. Post-infectious functional dyspepsia - A novel disease entity among functional gastrointestinal disorders - Relation to Helicobacter pylori infection? J Neurogastroenterol Motil. 2010;16:97–98.

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