Abstract
Functional dyspepsia is the most common reason for patients to experience chronic epigastric pain or discomfort. The causes of functional dyspepsia are multifactorial but Helicobacter pylori infection is one likely candidate. Infection with this bacterial pathogen clearly results in chronic mucosal inflammation in the stomach and duodenum, which, in turn, might lead to abnormalities in gastroduodenal motility and sensitivity. Chronic gastritis might also affect a variety of endocrine functions of the stomach including the production of the gastrointestinal hormones and neurotransmitters somatostatin, gastrin and ghrelin. Although these abnormalities might generate symptoms in some patients with functional dyspepsia, the clinical evidence needs to be critically evaluated before this hypothesis can be confirmed. A Cochrane review reported that eradication of H. pylori in these patients had a small but statistically significant long-term effect on symptom relief when compared with placebo, lasting at least 12 months after 1 week of eradication therapy. The efficacy of eradication therapy was seen in all symptom subtypes of functional dyspepsia, but was more marked in Asian than Western patients. This evidence has led to alterations in most of the major guidelines throughout the world, which now recommend H. pylori eradication in patients with functional dyspepsia if they test positive for this bacterium.
Key Points
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Helicobacter pylori infection is a major cause of gastritis and is associated with a variety of motility, endocrine and acid-secretory abnormalities that could drive the symptoms of functional dyspepsia
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In a meta-analysis of randomized controlled trials, H. pylori eradication had a small but statistically significant effect in controlling the symptoms of functional dyspepsia
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H. pylori eradication improves symptoms in patients with epigastric-pain-predominant and postprandial-distress-predominant functional dyspepsia
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The majority of guidelines recommend H. pylori eradication in at least a subset of patients with functional dyspepsia
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References
Talley, N. J., Phillips, S. F., Melton, J. 3rd, Wiltgen, C. & Zinsmeister, A. R. A patient questionnaire to identify bowel disease. Ann. Intern. Med. 111, 671–674 (1989).
Ford, A. C., Forman, D., Bailey, A. G., Axon, A. T. & Moayyedi, P. Effect of dyspepsia on survival: a longitudinal 10-year follow-up study. Am. J. Gastroenterol. 107, 912–921 (2012).
Ford, A. C., Forman, D., Bailey, A. G., Axon, A. T. & Moayyedi, P. Initial poor quality of life and new onset of dyspepsia: results from a longitudinal 10-year follow-up study. Gut 56, 321–327 (2007).
Ford, A. C., Marwaha, A., Lim, A. & Moayyedi, P. What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 8, 830–837 e831–e832 (2010).
Moayyedi, P. Dyspepsia. Curr. Opin. Gastroenterol. 28, 602–607 (2012).
Porter, C. K., Gormley, R., Tribble, D. R., Cash, B. D. & Riddle, M. S. The incidence and gastrointestinal infectious risk of functional gastrointestinal disorders in a healthy US adult population. Am. J. Gastroenterol. 106, 130–138 (2011).
Liebregts, T. et al. Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia. Am. J. Gastroenterol. 106, 1089–1098 (2011).
Ford, A. C. et al. Prevalence of uninvestigated dyspepsia 8 years after a large waterborne outbreak of bacterial dysentery: a cohort study. Gastroenterology 138, 1727–1736 (2010).
Bazzoli, F. et al. The Loiano–Monghidoro population-based study of Helicobacter pylori infection: prevalence by 13C-urea breath test and associated factors. Aliment. Pharmacol. Ther. 15, 1001–1007 (2001).
Suzuki, M. et al. H. pylori-eradication therapy increases RUNX3 expression in the glandular epithelial cells in enlarged-fold gastritis. J. Clin. Biochem. Nutr. 46, 259–264 (2010).
Suzuki, H., Nishizawa, T. & Hibi, T. Therapeutic strategies for functional dyspepsia and the introduction of the Rome III classification. J. Gastroenterol. 41, 513–523 (2006).
Suzuki, H., Hibi, T. & Marshall, B. J. Helicobacter pylori: present status and future prospects in Japan. J. Gastroenterol. 42, 1–15 (2007).
Suzuki, H., Nishizawa, T., Tsugawa, H., Mogami, S. & Hibi, T. Roles of oxidative stress in stomach disorders. J. Clin. Biochem. Nutr. 50, 35–39 (2012).
Suzuki, H., Suzuki, M., Imaeda, H. & Hibi, T. Helicobacter pylori and microcirculation. Microcirculation 16, 547–558 (2009).
Suzuki, S. et al. Delayed gastric emptying and disruption of the interstitial cells of Cajal network after gastric ischaemia and reperfusion. Neurogastroenterol. Motil. 22, 585–593 (2010).
Mogami, S. et al. Reduced ghrelin production induced anorexia after rat gastric ischemia and reperfusion. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G359–G364 (2012).
Savarino, E., Zentilin, P., Dulbecco, P., Malesci, A. & Savarino, V. The role of acid in functional dyspepsia. Am. J. Gastroenterol. 106, 1168 (2011).
El-Omar, E., Penman, I., Dorrian, C. A., Ardill, J. E. & McColl, K. E. Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer. Gut 34, 1060–1065 (1993).
Amieva, M. R. & El-Omar, E. M. Host–bacterial interactions in Helicobacter pylori infection. Gastroenterology 134, 306–323 (2008).
Hurlimann, S. et al. Effects of Helicobacter pylori on gastritis, pentagastrin-stimulated gastric acid secretion, and meal-stimulated plasma gastrin release in the absence of peptic ulcer disease. Am. J. Gastroenterol. 93, 1277–1285 (1998).
McColl, K. E., El-Omar, E. & Gillen, D. Interactions between H. pylori infection, gastric acid secretion and anti-secretory therapy. Br. Med. Bull. 54, 121–138 (1998).
Koike, T. et al. Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion. Gut 49, 330–334 (2001).
Moss, S. F., Legon, S., Bishop, A. E., Polak, J. M. & Calam, J. Effect of Helicobacter pylori on gastric somatostatin in duodenal ulcer disease. Lancet 340, 930–932 (1992).
Odum, L., Petersen, H. D., Andersen, I. B., Hansen, B. F. & Rehfeld, J. F. Gastrin and somatostatin in Helicobacter pylori infected antral mucosa. Gut 35, 615–618 (1994).
Kamada, T. et al. The association between antral G and D cells and mucosal inflammation, atrophy, and Helicobacter pylori infection in subjects with normal mucosa, chronic gastritis, and duodenal ulcer. Am. J. Gastroenterol. 93, 748–752 (1998).
Calam, J., Gibbons, A., Healey, Z. V., Bliss, P. & Arebi, N. How does Helicobacter pylori cause mucosal damage? Its effect on acid and gastrin physiology. Gastroenterology 113, S43–S49 (1997).
Mulholland, G. et al. Helicobacter pylori related hypergastrinaemia is the result of a selective increase in gastrin 17. Gut 34, 757–761 (1993).
Liu, Y., Vosmaer, G. D., Tytgat, G. N., Xiao, S. D. & Ten Kate, F. J. Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis. J. Clin. Pathol. 58, 927–931 (2005).
Konturek, J. W., Bielanski, W., Konturek, S. J. & Domschke, W. Eradication of Helicobacter pylori and gastrin-somatostatin link in duodenal ulcer patients. J. Physiol. Pharmacol. 47, 161–175 (1996).
Suzuki, H. et al. Helicobacter pylori infection modifies gastric and plasma ghrelin dynamics in Mongolian gerbils. Gut 53, 187–194 (2004).
Osawa, H. et al. Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori. J. Clin. Endocrinol. Metab. 90, 10–16 (2005).
Suzuki, H. et al. Plasma ghrelin concentration correlates with the levels of serum pepsinogen I and pepsinogen I/II ratio--a possible novel and non-invasive marker for gastric atrophy. Hepatogastroenterology 51, 1249–1254 (2004).
Isomoto, H. et al. Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am. J. Gastroenterol. 100, 1711–1720 (2005).
Dong, C. X. & Brubaker, P. L. Ghrelin, the proglucagon-derived peptides and peptide YY in nutrient homeostasis. Nat. Rev. Gastroenterol. Hepatol. 9, 705–715 (2012).
Mori, M. et al. Intravenous ghrelin administration enhances gastric acid secretion—evaluation using wireless pH capsule. Aliment. Pharmacol. Ther. 24, 96–103 (2006).
Arai, M. et al. Rikkunshito improves the symptoms in patients with functional dyspepsia, accompanied by an increase in the level of plasma ghrelin. Hepatogastroenterology 59, 62–66 (2012).
Iijima, K. et al. Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication. Gut 46, 20–26 (2000).
Osawa, H. et al. Helicobacter pylori eradication induces marked increase in H+/K+-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa. Gut 55, 152–157 (2006).
Osawa, H. et al. Changes in plasma ghrelin levels, gastric ghrelin production, and body weight after Helicobacter pylori cure. J. Gastroenterol. 41, 954–961 (2006).
Masaoka, T. et al. Long-term strict monitoring of plasma ghrelin and other serological markers of gastric diseases after Helicobacter pylori eradication. Hepatogastroenterology 52, 1–4 (2005).
Tatsuguchi, A. et al. Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa. Am. J. Gastroenterol. 99, 2121–2127 (2004).
Jang, E. J. et al. The influence of the eradication of Helicobacter pylori on gastric ghrelin, appetite, and body mass index in patients with peptic ulcer disease. J. Gastroenterol. Hepatol. 23 (Suppl. 2), S278–S285 (2008).
Choe, Y. H. et al. Ghrelin levels in gastric mucosa before and after eradication of Helicobacter pylori. Gut Liver 1, 132–137 (2007).
Nogueiras, R., Williams, L. M. & Dieguez, C. Ghrelin: new molecular pathways modulating appetite and adiposity. Obes. Facts 3, 285–292 (2010).
Miyaji, H. et al. The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia. Aliment. Pharmacol. Ther. 13, 1473–1480 (1999).
Matsumoto, Y. et al. Relation between histologic gastritis and gastric motility in Japanese patients with functional dyspepsia: evaluation by transabdominal ultrasonography. J. Gastroenterol. 43, 332–337 (2008).
Kachi, M. et al. Effects of Helicobacter pylori eradication therapy on gastric emptying measured using the 13C-octanoic acid breath test and the acetaminophen method. J. Gastroenterol. Hepatol. 21, 824–830 (2006).
Saito, Y. et al. Dysfunctional gastric emptying with down-regulation of muscle-specific microRNAs in Helicobacter pylori-infected mice. Gastroenterology 140, 189–198 (2011).
Tack, J. et al. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment. Pharmacol. Ther. 22, 847–853 (2005).
Murray, C. D. et al. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut 54, 1693–1698 (2005).
US National Library of Medicine. ClinicalTrials.gov [online], (2012).
Hall, W., Buckley, M., Crotty, P. & O'Morain, C. A. Gastric mucosal mast cells are increased in Helicobacter pylori-negative functional dyspepsia. Clin. Gastroenterol. Hepatol. 1, 363–369 (2003).
Miyamoto, M. et al. Nodular gastritis in adults is caused by Helicobacter pylori infection. Dig. Dis. Sci. 48, 968–975 (2003).
Dwivedi, M., Misra, S. P. & Misra, V. Nodular gastritis in adults: clinical features, endoscopic appearance, histopathological features, and response to therapy. J. Gastroenterol. Hepatol. 23, 943–947 (2008).
Murayama, Y. et al. Morphological and functional restoration of parietal cells in Helicobacter pylori associated enlarged fold gastritis after eradication. Gut 45, 653–661 (1999).
Matsunari, O. et al. Association between Helicobacter pylori virulence factors and gastroduodenal diseases in Okinawa, Japan. J. Clin. Microbiol. 50, 876–883 (2012).
Suzuki, H., Nishizawa, T. & Hibi, T. Can Helicobacter pylori-associated dyspepsia be categorized as functional dyspepsia? J. Gastroenterol. Hepatol. 26 (Suppl. 3), 42–45 (2011).
Suzuki, H., Matsuzaki, J. & Hibi, T. What is the difference between Helicobacter pylori-associated dyspepsia and functional dyspepsia? J. Neurogastroenterol. Motil. 17, 124–130 (2011).
Sugano, K. Should we still subcategorize Helicobacter pylori-associated dyspepsia as functional disease? J. Neurogastroenterol. Motil. 17, 366–371 (2011).
Yagi, K., Aruga, Y., Nakamura, A. & Sekine, A. Regular arrangement of collecting venules (RAC): a characteristic endoscopic feature of Helicobacter pylori-negative normal stomach and its relationship with esophago-gastric adenocarcinoma. J. Gastroenterol. 40, 443–452 (2005).
Anagnostopoulos, G. K. et al. High-resolution magnification endoscopy can reliably identify normal gastric mucosa, Helicobacter pylori-associated gastritis, and gastric atrophy. Endoscopy 39, 202–207 (2007).
Suzuki, H. et al. Current consensus on the diagnosis and treatment of H. pylori-associated gastroduodenal disease. Keio J. Med. 52, 163–173 (2003).
McColl, K. et al. Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia. N. Engl. J. Med. 339, 1869–1874 (1998).
Blum, A. L. et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. Omeprazole plus Clarithromycin and Amoxicillin effect one year after treatment (OCAY) Study Group. N. Engl. J. Med. 339, 1875–1881 (1998).
Laine, L., Schoenfeld, P. & Fennerty, M. B. Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta-analysis of randomized, controlled trials. Ann. Intern. Med. 134, 361–369 (2001).
Moayyedi, P. et al. Systematic review and economic evaluation of Helicobacter pylori eradication treatment for non-ulcer dyspepsia. Dyspepsia Review Group. BMJ 321, 659–664 (2000).
Moayyedi, P., Deeks, J., Talley, N. J., Delaney, B. & Forman, D. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am. J. Gastroenterol. 98, 2621–2626 (2003).
Mazzoleni, L. E. et al. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch. Intern. Med. 171, 1929–1936 (2011).
Moayyedi, P. Helicobacter pylori eradication for functional dyspepsia: what are we treating?: comment on “Helicobacter pylori eradication in functional dyspepsia”. Arch. Intern. Med. 171, 1936–1937 (2011).
Moayyedi, P. et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD002096. doi:10.1002/14651858.CD002096.pub5 (2006).
Jin, X. & Li, Y. M. Systematic review and meta-analysis from Chinese literature: the association between Helicobacter pylori eradication and improvement of functional dyspepsia. Helicobacter 12, 541–546 (2007).
Moayyedi, P., Delaney, B. C., Vakil, N., Forman, D. & Talley, N. J. The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology 127, 1329–1337 (2004).
Moayyedi, P. et al. Systematic review: antacids, H2-receptor antagonists, prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia. Aliment. Pharmacol. Ther. 17, 1215–1227 (2003).
Abraham, N. S., Moayyedi, P., Daniels, B. & Veldhuyzen Van Zanten, S. J. Systematic review: the methodological quality of trials affects estimates of treatment efficacy in functional (non-ulcer) dyspepsia. Aliment. Pharmacol. Ther. 19, 631–641 (2004).
Kindt, S. et al. Longitudinal and cross-sectional factors associated with long-term clinical course in functional dyspepsia: a 5-year follow-up study. Am. J. Gastroenterol. 106, 340–348 (2011).
Moayyedi, P. & Leontiadis, G. I. The risks of PPI therapy. Nat. Rev. Gastroenterol. Hepatol. 9, 132–139 (2012).
Basu, P. P. et al. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am. J. Gastroenterol. 106, 1970–1975 (2011).
Watson, J. B. & Moss, S. F. Will H. pylori stagger under the weight of this LOAD? A novel but expensive eradication regimen. Am. J. Gastroenterol. 106, 1976–1977 (2011).
Geeraerts, B. & Tack, J. Functional dyspepsia: past, present, and future. J. Gastroenterol. 43, 251–255 (2008).
Tack, J., Masaoka, T. & Janssen, P. Functional dyspepsia. Curr. Opin. Gastroenterol. 27, 549–557 (2011).
Talley, N. J., Janssens, J., Lauritsen, K., Racz, I. & Bolling-Sternevald, E. Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months' follow up. The Optimal Regimen Cures Helicobacter Induced Dyspepsia (ORCHID) Study Group. BMJ 318, 833–837 (1999).
Hsu, P. I. et al. Eradication of Helicobacter pylori prevents ulcer development in patients with ulcer-like functional dyspepsia. Aliment. Pharmacol. Ther. 15, 195–201 (2001).
Gwee, K. A. et al. The response of Asian patients with functional dyspepsia to eradication of Helicobacter pylori infection. Eur. J. Gastroenterol. Hepatol. 21, 417–424 (2009).
Bruley Des Varannes, S. et al. There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia. Aliment. Pharmacol. Ther. 15, 1177–1185 (2001).
Lan, L. et al. Symptom-based tendencies of Helicobacter pylori eradication in patients with functional dyspepsia. World J. Gastroenterol. 17, 3242–3247 (2011).
Lee, K. J., Vos, R., Janssens, J. & Tack, J. Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G278–G284 (2004).
Ang, D. et al. Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man. Neurogastroenterol. Motil. 21, 528–533 (2009).
Lacy, B. E. et al. Review article: current treatment options and management of functional dyspepsia. Aliment. Pharmacol. Ther. 36, 3–15 (2012).
Bytzer, P. et al. Diagnosis and treatment of Helicobacter pylori infection. Dan. Med. Bull. 58, C4271 (2011).
Jee, S. R. et al. Guidelines for the treatment of functional dyspepsia [Korean]. Korean J. Gastroenterol. 57, 67–81 (2011).
Fischbach, W. Short version of the S3 (level 3) guideline “Helicobacter pylori and gastroduodenal ulcer disease” from the German Society for Digestive and Metabolic Diseases [German]. Dtsch. Med. Wochenschr. 134, 1830–1834 (2009).
Chey, W. D. & Wong, B. C. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am. J. Gastroenterol. 102, 1808–1825 (2007).
Fock, K. M. et al. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J. Gastroenterol. Hepatol. 24, 1587–1600 (2009).
Miwa, H. et al. Asian consensus report on functional dyspepsia. J. Gastroenterol. Hepatol. 27, 626–641 (2012).
Asaka, M. et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter 15, 1–20 (2010).
Malfertheiner, P. et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. Gut 61, 646–664 (2012).
Ford, A. C., Delaney, B. C., Forman, D. & Moayyedi, P. Eradication therapy in Helicobacter pylori positive peptic ulcer disease: systematic review and economic analysis. Am. J. Gastroenterol. 99, 1833–1855 (2004).
Sanchez-Delgado, J. et al. Has H. pylori prevalence in bleeding peptic ulcer been underestimated? A meta-regression. Am. J. Gastroenterol. 106, 398–405 (2011).
Gonzalez, C. A. et al. Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long-term follow-up in a high-risk area in Spain. Am. J. Gastroenterol. 106, 867–874 (2011).
Acknowledgements
This work was supported by a Health and Labour Sciences Research Grant for Research on Health Technology Assessment (Clinical Research Promotion No. 47 to H. Suzuki) and a grant from the Smoking Research Foundation (to H. Suzuki), and the Keio Gijuku Academic Development Fund (to H. Suzuki).
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H. Suzuki has accepted research grants and honoraria from Astellas, AstraZeneca, Eisai, Otsuka, Daiichi–Sankyo, Dainippon–Sumitomo, Takeda, Tsumura and Zeria over the past 5 years. P. Moayyedi has accepted honoraria from AstraZeneca, Abbott, Pendopharm, Shire and Takeda over the past 5 years. His endowed Chair is partially funded by an unrestricted donation to McMaster University from AstraZeneca.
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Suzuki, H., Moayyedi, P. Helicobacter pylori infection in functional dyspepsia. Nat Rev Gastroenterol Hepatol 10, 168–174 (2013). https://doi.org/10.1038/nrgastro.2013.9
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DOI: https://doi.org/10.1038/nrgastro.2013.9
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