Abstract
Background
Ghrelin has been indicated as one of the etiological factors in functional dyspepsia (FD).
Methods
We analyzed 179 patients with FD (based on the Rome III criteria) and 103 asymptomatic healthy individuals (controls) who had undergone endoscopy at Seoul National University Bundang Hospital from February 2011 to June 2014. FD patients were classified into three groups by means of a self-reported questionnaire: patients with postprandial distress syndrome (PDS; n = 49), patients with epigastric pain syndrome (EPS; n = 45), and patients with a combination of these two types (mixed group; n = 85). The fasting blood levels of acyl ghrelin and desacyl ghrelin and messenger RNA (mRNA) expression of preproghrelin in the fundic mucosa were measured by ELISAs and reverse transcription quantitative real-time PCR, respectively. One year after participant enrollment, they were measured again in 79 participants and the changes in the values were compared according to Helicobacter pylori eradication or symptom response.
Results
Plasma acyl ghrelin level was lower in the PDS group than in the control and EPS groups (control group 14.1 fmol/mL, PDS group 8.9 fmol/mL, EPS group 13.8 fmol/mL, mixed group 11.3 fmol/mL; P = 0.003 and P = 0.012, respectively). One year after the eradication of H. pylori, plasma acyl ghrelin level was increased and gastric preproghrelin mRNA expression was upregulated (P = 0.004 and P < 0.001, respectively). Patients with abatement of symptoms demonstrated an increase in plasma acyl ghrelin level (from 11.51 to 21.00 fmol/L, P = 0.040).
Conclusions
Our results suggest that plasma acyl ghrelin plays a role in the development of PDS. H. pylori eradication upregulates preproghrelin mRNA expression and increases plasma acyl ghrelin level, contributing to the abatement of PDS symptoms.
Abbreviations
- BMI:
-
Body mass index
- EPS:
-
Epigastric pain syndrome
- FD:
-
Functional dyspepsia
- GADPH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- GI:
-
Gastrointestinal
- mRNA:
-
Messenger RNA
- PDS:
-
Postprandial distress syndrome
- PG I:
-
Pepsinogen I
- PG II:
-
Pepsinogen II
- PPI:
-
Proton-pump inhibitor
References
Wu JC. Psychological co-morbidity in functional gastrointestinal disorders: epidemiology, mechanisms and management. J Neurogastroenterol Motil. 2012;18:13–8.
Stanghellini V, Tosetti C, Paternico A, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology. 1996;110:1036–42.
Tack J, Caenepeel P, Fischler B, et al. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 2001;121:526–35.
Hwang SW, Kim N, Jung HK, et al. The association of SLC6A4 5-HTTLPR and TRPV1 945G>C with functional dyspepsia in Korea. J Gastroenterol Hepatol. 2014;29:1770–7.
Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–76.
Khoo J, Rayner CK, Feinle-Bisset C, et al. Gastrointestinal hormonal dysfunction in gastroparesis and functional dyspepsia. Neurogastroenterol Motil. 2010;22:1270–8.
Akamizu T, Iwakura H, Ariyasu H, et al. Ghrelin and functional dyspepsia. Int J Pept. 2010. doi:10.1155/2010/548457.
Jeffery PL, McGuckin MA, Linden SK. Endocrine impact of Helicobacter pylori: focus on ghrelin and ghrelin o-acyltransferase. World J Gastroenterol. 2011;17:1249–60.
Wren A, Seal L, Cohen M, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992–5.
Goebel-Stengel M, Hofmann T, Elbelt U, et al. The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index. Peptide. 2013;43:10–3.
Bednarek MA, Feighner SD, Pong SS, et al. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem. 2000;43:4370–6.
Van Der Lely AJ, Tschop M, Heiman ML, et al. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev. 2004;25:426–57.
Shindo T, Futagami S, Hiratsuka T, et al. Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease. Digestion. 2009;79:65–72.
Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006;130:1377–90.
Suzuki H, Moayyedi P. Helicobacter pylori infection in functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2013;10:168–74.
Budzyński J, Kłopocka M. Brain-gut axis in the pathogenesis of Helicobacter pylori infection. World J Gastroenterol. 2014;20:5212–25.
Isomoto H, Ueno H, Saenko VA, et al. Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am J Gastroenterol. 2005;100:1711–20.
Boltin D, Niv Y. Ghrelin, Helicobacter pylori and body mass: is there an association? Isr Med Assoc J. 2012;14:130–2.
Nweneka CV, Prentice AM. Helicobacter pylori infection and circulating ghrelin levels-a systematic review. BMC gastroenterol. 2011;11:7.
Song KH, Jung HK, Min BH, et al. Development and validation of the Korean Rome III questionnaire for diagnosis of functional gastrointestinal disorders. J Neurogastroenterol Motil. 2013;19:509–15.
Noh YW, Jung HK, Kim SE, Jung S. Overlap of erosive and non-erosive reflux diseases with functional gastrointestinal disorders according to Rome III criteria. J Neurogastroenterol Motil. 2010;16:148–56.
Kim SE, Park YS, Kim N, et al. Effect of Helicobacter pylori eradication on functional dyspepsia. J Neurogastroenterol Motil. 2013;19:233–43.
Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis: the updated Sydney system. Am J Surg Pathol. 1996;20:1161–81.
Fung JN, Seim I, Wang D, et al. Expression and in vitro functions of the ghrelin axis in endometrial cancer. Horm Cancer. 2010;1:245–55.
Kim HY, Kim N, Kang JM, et al. Clinical meaning of pepsinogen test and Helicobacter pylori serology in the health check-up population in Korea. Eur J Gastroenterol Hepatol. 2009;21:606–12.
Suzuki H, Matsuzaki J, Fukushima Y, et al. Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia—a multicenter, double-blind, randomized, placebo-controlled study. Neurogastroenterol Motil. 2014;26:950–61.
Kang JM, Kim N, Yoo JY, et al. The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea. Helicobacter. 2008;13:146–56.
Shin A, Camilleri M, Busciglio I, et al. The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus. Clin Gastroenterol Hepatol. 2013;11:1453–9.e4.
Takiguchi S, Hiura Y, Takahashi T, et al. Effect of rikkunshito, a Japanese herbal medicine, on gastrointestinal symptoms and ghrelin levels in gastric cancer patients after gastrectomy. Gastric Cancer. 2013;16:167–74.
Arai M, Matsumura T, Tsuchiya N, et al. Rikkunshito improves the symptoms in patients with functional dyspepsia, accompanied by an increase in the level of plasma ghrelin. Hepatogastroenterology. 2011;59:62–6.
Nishizawa T, Suzuki H, Nomoto Y, et al. Enhanced plasma ghrelin levels in patients with functional dyspepsia. Aliment Pharmacol Ther. 2006;24:104–10.
Shinomiya T, Fukunaga M, Akamizu T, et al. Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients. Scand J Gastroenterol. 2005;40:648–53.
Vakil N, Halling K, Ohlsson L, et al. Symptom overlap between postprandial distress and epigastric pain syndromes of the Rome III dyspepsia classification. Am J Gastroenterol. 2013;108:767–74.
Banks WA, Tschöp M, Robinson SM, et al. Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther. 2002;302:822–7.
Luckman SM, Rosenzweig I, Dickson SL. Activation of arcuate nucleus neurons by systemic administration of leptin and growth hormone-releasing peptide-6 in normal and fasted rats. Neuroendocrinology. 1999;70:93–100.
Suzuki H, Matsuzaki J, Hibi T. Ghrelin and oxidative stress in gastrointestinal tract. J Clin Biochem Nutr. 2011;48:122–5.
Suzuki H, Matsuzaki J, Hibi T. What is the difference between Helicobacter pylori-associated dyspepsia and functional dyspepsia? J Neurogastroenterol Motil. 2011;17:124–30.
Isomoto H, Ueno H, Nishi Y, et al. Circulating ghrelin levels in patients with various upper gastrointestinal diseases. Dig Dis Sci. 2005;50:833–8.
Suzuki H, Masaoka T, Hosoda H, et al. Helicobacter pylori infection modifies gastric and plasma ghrelin dynamics in Mongolian gerbils. Gut. 2004;53:187–94.
Roper J, Francois F, Shue PL, et al. Leptin and ghrelin in relation to Helicobacter pylori status in adult males. J Clin Endocrinol Metab. 2008;93:2350–7.
Osawa H, Kita H, Ohnishi H, et al. Changes in plasma ghrelin levels, gastric ghrelin production, and body weight after Helicobacter pylori cure. J Gastroenterol. 2006;41:954–61.
Czesnikiewicz-Guzik M, Loster B, Bielanski W, et al. Implications of oral Helicobacter pylori for the outcome of its gastric eradication therapy. J Clin Gastroenterol. 2007;41:145–51.
Kawashima J, Ohno S, Sakurada T, et al. Circulating acylated ghrelin level decreases in accordance with the extent of atrophic gastritis. J Gastroenterol. 2009;44:1046–54.
Moayyedi P, Soo S, Deeks JJ, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;(2):CD002096.
Miwa H, Kusano M, Arisawa T, et al. Evidence-based clinical practice guidelines for functional dyspepsia. J Gastroenterol. 2015;50:125–39.
Miwa H, Hirai S, Nagahara A, et al. Cure of Helicobacter pylori infection does not improve symptoms in non-ulcer dyspepsia patients—a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2000;14:317–24.
Gwee K-A, Teng L, Wong R-K, et al. The response of Asian patients with functional dyspepsia to eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2009;21:327–34.
Barkan AL, Dimaraki EV, Jessup SK, et al. Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab. 2003;88:2180–4.
Acknowledgments
This work was supported by a Korean Society of Neurogastroenterology and Motility grant in 2011. The authors are indebted to J. Patrick Barron, Seoul National University Bundang Hospital, for his pro bono editing of the manuscript.
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Choi, Y.J., Kim, N., Yoon, H. et al. Increase in plasma acyl ghrelin levels is associated with abatement of dyspepsia following Helicobacter pylori eradication. J Gastroenterol 51, 548–559 (2016). https://doi.org/10.1007/s00535-015-1124-6
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DOI: https://doi.org/10.1007/s00535-015-1124-6