Changes in duodenal enteroendocrine cells in patients with irritable bowel syndrome following dietary guidance

Tarek Mazzawi, Magdy El-Salhy, Tarek Mazzawi, Magdy El-Salhy

Abstract

The densities of enteroendocrine cells are abnormal in patients with irritable bowel syndrome (IBS); however, they tend to change toward normal levels in stomach, ileum, and colon following dietary guidance. The aim was to identify the types of duodenal enteroendocrine cells affected after receiving dietary guidance in the same group of patients with IBS. Fourteen patients with IBS and 14 control subjects were included. The patients received three sessions of dietary guidance. Both groups underwent gastroscopies at baseline, and again for the patients after 3-9 months (median, four months) from receiving dietary guidance. Tissue biopsies were collected from the descending part of the duodenum and were immunostained for all the types of enteroendocrine cells and were then quantified by using computerized image analysis. Using the Kruskal-Wallis non-parametric test with Dunn's test as a post-test, the results showed a significant difference in the secretin cell densities between control subjects and patients with IBS prior to and following dietary guidance ( P = 0.0001 and 0.011, respectively). The corresponding P values for cholecystokinin (CCK) cell densities were 0.03 and 0.42, respectively; gastric inhibitory peptide (GIP) cell densities were 0.06 and 0.43, respectively; serotonin cell densities were <0.0001 and 0.002, respectively; and for somatostatin cell densities were <0.0001 and 0.052, respectively. The Paired t-test showed a significant difference only in the serotonin ( P = 0.03) and somatostatin ( P < 0.0001) cell densities between IBS patients prior to and following dietary guidance. The changes in the cell densities of secretin, CCK, and GIP were not significant between IBS patients prior to and following dietary guidance. In conclusion, the densities of several duodenal enteroendocrine cells in IBS patients changed toward the values measured in control subjects following dietary guidance. The changes in serotonin and somatostatin cell densities may have contributed to the improvements in IBS symptoms, particularly pain and diarrhea. Impact statement Several contributing factors to the symptomology of irritable bowel syndrome (IBS) have been identified, such as abnormal densities of enteroendocrine cells and diet; however, the interactions between these factors have not been studied yet. The current study aims at exploring the dynamic changes between these two factors by studying the effect of using low fermentable oligo-, di-, monosaccharides and polyol (FODMAP) diet (known to improve IBS symptoms) through dietary guidance on the enteroendocrine cell densities in the duodenum. The findings showed that the densities of different enteroendocrine cells in the duodenum were abnormal before the patients received dietary guidance and tend to change/normalize after receiving guidance, which may have contributed in improving the symptoms of IBS. These findings highlight the importance of enteroendocrine cells in IBS pathophysiology and the mechanism behind the positive effect of low FODMAP dietary guidance in improving IBS symptoms and its usage as first step in the line of IBS management.

Keywords: Computerized image analysis; diet; duodenum; enteroendocrine cells; immunohistochemistry; irritable bowel syndrome.

Figures

Figure 1
Figure 1
Study flowchart
Figure 2
Figure 2
Secretin cell densities in the duodenum of IBS patients before and after receiving dietary guidance. The dashed lines labeled ‘a’ and ‘c’ indicate the upper and lower limits of the 95% confidence interval of the secretin cell density in control subjects, respectively, while line ‘b’ indicates the mean density. IBS: irritable bowel syndrome
Figure 3
Figure 3
CCK cell densities in the duodenum of IBS patients before and after receiving dietary guidance. The dashed lines labeled ‘a’ and ‘c’ indicate the upper and lower limits of the 95% confidence interval of the CCK cell density in control subjects, respectively, while line ‘b’ indicates the mean density. CCK: cholecystokinin; IBS: irritable bowel syndrome
Figure 4
Figure 4
GIP cell densities in the duodenum of IBS patients before and after receiving dietary guidance. The dashed lines labeled ‘a’ and ‘c’ indicate the upper and lower limits of the 95% confidence interval of the GIP cell density in control subjects, respectively, while line ‘b’ indicates the mean density. GIP: gastric inhibitory peptide; IBS: irritable bowel syndrome
Figure 5
Figure 5
Serotonin cell densities in the duodenum of IBS patients before and after receiving dietary guidance. The dashed lines labeled ‘a’ and ‘c’ indicate the upper and lower limits of the 95% confidence interval of the serotonin cell density in control subjects, respectively, while line ‘b’ indicates the mean density. *P 

Figure 6

Somatostatin cell densities in the…

Figure 6

Somatostatin cell densities in the duodenum of IBS patients before and after receiving…

Figure 6
Somatostatin cell densities in the duodenum of IBS patients before and after receiving dietary guidance. The dashed lines labeled ‘a’ and ‘c’ indicate the upper and lower limits of the 95% confidence interval of the somatostatin cell density in control subjects, respectively, while line ‘b’ indicates the mean density. ****P 

Figure 7

Somatostatin cells in the duodenum…

Figure 7

Somatostatin cells in the duodenum of a control subject (a) and of an…

Figure 7
Somatostatin cells in the duodenum of a control subject (a) and of an IBS patient before (b) and after (c) receiving dietary guidance. IBS: irritable bowel syndrome
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References
    1. El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. Irritable bowel syndrome, New York, NY: Nova Science Publisher, 2012.
    1. El-Salhy M. Irritable bowel syndrome: diagnosis and pathogenesis. World J Gastroenterol 2012; 18: 5151–63. - PMC - PubMed
    1. El-Salhy M. Recent developments in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2015; 21: 7621–36. - PMC - PubMed
    1. Simren M, Mansson A, Langkilde AM, Svedlund J, Abrahamsson H, Bengtsson U, Bjornsson ES. Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 2001; 63: 108–15. - PubMed
    1. Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome—etiology, prevalence and consequences. Eur J Clin Nutr 2006; 60: 667–72. - PubMed
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Figure 6
Figure 6
Somatostatin cell densities in the duodenum of IBS patients before and after receiving dietary guidance. The dashed lines labeled ‘a’ and ‘c’ indicate the upper and lower limits of the 95% confidence interval of the somatostatin cell density in control subjects, respectively, while line ‘b’ indicates the mean density. ****P 

Figure 7

Somatostatin cells in the duodenum…

Figure 7

Somatostatin cells in the duodenum of a control subject (a) and of an…

Figure 7
Somatostatin cells in the duodenum of a control subject (a) and of an IBS patient before (b) and after (c) receiving dietary guidance. IBS: irritable bowel syndrome
All figures (7)
Figure 7
Figure 7
Somatostatin cells in the duodenum of a control subject (a) and of an IBS patient before (b) and after (c) receiving dietary guidance. IBS: irritable bowel syndrome

References

    1. El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. Irritable bowel syndrome, New York, NY: Nova Science Publisher, 2012.
    1. El-Salhy M. Irritable bowel syndrome: diagnosis and pathogenesis. World J Gastroenterol 2012; 18: 5151–63.
    1. El-Salhy M. Recent developments in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2015; 21: 7621–36.
    1. Simren M, Mansson A, Langkilde AM, Svedlund J, Abrahamsson H, Bengtsson U, Bjornsson ES. Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 2001; 63: 108–15.
    1. Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome—etiology, prevalence and consequences. Eur J Clin Nutr 2006; 60: 667–72.
    1. El-Salhy M, Gundersen D. Diet in irritable bowel syndrome. Nutr J 2015; 14: 36–36.
    1. El-Salhy M, Ostgaard H, Gundersen D, Hatlebakk JG, Hausken T. The role of diet in the pathogenesis and management of irritable bowel syndrome (Review). Int J Mol Med 2012; 29: 723–31.
    1. Ostgaard H, Hausken T, Gundersen D, El-Salhy M. Diet and effects of diet management on quality of life and symptoms in patients with irritable bowel syndrome. Mol Med Rep 2012; 5: 1382–90.
    1. Biesiekierski JR, Rosella O, Rose R, Liels K, Barrett JS, Shepherd SJ, Gibson PR, Muir JG. Quantification of fructans, galacto-oligosacharides and other short-chain carbohydrates in processed grains and cereals. J Hum Nutr Diet 2011; 24: 154–76.
    1. Muir JG, Rose R, Rosella O, Liels K, Barrett JS, Shepherd SJ, Gibson PR. Measurement of short-chain carbohydrates in common Australian vegetables and fruits by high-performance liquid chromatography (HPLC). J Agric Food Chem 2009; 57: 554–65.
    1. Muir JG, Shepherd SJ, Rosella O, Rose R, Barrett JS, Gibson PR. Fructan and free fructose content of common Australian vegetables and fruit. J Agric Food Chem 2007; 55: 6619–27.
    1. Mazzawi T, Hausken T, Gundersen D, El-Salhy M. Effects of dietary guidance on the symptoms, quality of life and habitual dietary intake of patients with irritable bowel syndrome. Mol Med Rep 2013; 8: 845–52.
    1. El-Salhy M, Gundersen D, Gilja OH, Hatlebakk JG, Hausken T. Is irritable bowel syndrome an organic disorder? World J Gastroenterol 2014; 20: 384–400.
    1. Tolhurst G, Reimann F, Gribble FM. Intestinal sensing of nutrients. Handb Exp Pharmacol 2012; 209: 309–35.
    1. Parker HE, Reimann F, Gribble FM. Molecular mechanisms underlying nutrient-stimulated incretin secretion. Expert Rev Mol Med 2010; 12: e1–e1.
    1. Raybould HE. Nutrient sensing in the gastrointestinal tract: possible role for nutrient transporters. J Physiol Biochem 2008; 64: 349–56.
    1. Sternini C, Anselmi L, Rozengurt E. Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr Opin Endocrinol Diabetes Obes 2008; 15: 73–78.
    1. Buchan AM. Nutrient tasting and signaling mechanisms in the gut III. Endocrine cell recognition of luminal nutrients. Am J Physiol 1999; 277: G1103–7.
    1. Montero-Hadjadje M, Elias S, Chevalier L, Benard M, Tanguy Y, Turquier V, Galas L, Yon L, Malagon MM, Driouich A, Gasman S, Anouar Y. Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides. J Biol Chem 2009; 284: 12420–31.
    1. El-Salhy M, Gilja OH, Gundersen D, Hatlebakk JG, Hausken T. Endocrine cells in the ileum of patients with irritable bowel syndrome. World J Gastroenterol 2014; 20: 2383–91.
    1. El-Salhy M, Gilja OH, Gundersen D, Hausken T. Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome. World J Gastrointest Endosc 2014; 6: 176–85.
    1. El-Salhy M, Gundersen D, Hatlebakk JG, Gilja OH, Hausken T. Abnormal rectal endocrine cells in patients with irritable bowel syndrome. Regul Pept 2014; 188: 60–5.
    1. El-Salhy M, Gundersen D, Ostgaard H, Lomholt-Beck B, Hatlebakk JG, Hausken T. Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome. Dig Dis Sci 2012; 57: 873–8.
    1. El-Salhy M, Lillebo E, Reinemo A, Salmelid L. Ghrelin in patients with irritable bowel syndrome. Int J Mol Med 2009; 23: 703–7.
    1. El-Salhy M, Lomholt-Beck B, Hausken T. Chromogranin A as a possible tool in the diagnosis of irritable bowel syndrome. Scand J Gastroenterol 2010; 45: 1435–9.
    1. El-Salhy M, Vaali K, Dizdar V, Hausken T. Abnormal small-intestinal endocrine cells in patients with irritable bowel syndrome. Dig Dis Sci 2010; 55: 3508–13.
    1. Mazzawi T, Gundersen D, Hausken T, El-Salhy M. Increased gastric chromogranin a cell density following changes to diets of patients with irritable bowel syndrome. Mol Med Rep 2014; 10: 2322–36.
    1. Mazzawi T, Gundersen D, Hausken T, El-Salhy M. Increased chromogranin a cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance. Gastroenterol Res Pract 2015; 2015: 823897–823897.
    1. Mazzawi T, Hausken T, Gundersen D, El-Salhy M. Effect of dietary management on the gastric endocrine cells in patients with irritable bowel syndrome. Eur J Clin Nutr 2015; 69: 519–24.
    1. Mazzawi T, Hausken T, Gundersen D, El-Salhy M. Dietary guidance normalizes large intestinal endocrine cell densities in patients with irritable bowel syndrome. Eur J Clin Nutr 2016; 70: 175–81.
    1. Mazzawi T, El-Salhy M. Changes in small intestinal chromogranin A-immunoreactive cell densities in patients with irritable bowel syndrome after receiving dietary guidance. Int J Mol Med 2016; 37: 1247–53.
    1. Mazzawi T, El-Salhy M. Dietary guidance and ileal enteroendocrine cells in patients with irritable bowel syndrome. Exp Ther Med 2016; 12: 1398–1404.
    1. Taupenot L, Harper KL, O'Connor DT. The chromogranin-secretogranin family. N Engl J Med 2003; 348: 1134–49.
    1. Wiedenmann B, Huttner WB. Synaptophysin and chromogranins/secretogranins—widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch B Cell Pathol Incl Mol Pathol 1989; 58: 95–121.
    1. Deftos LJ. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev 1991; 12: 181–7.
    1. Roalfe AK, Roberts LM, Wilson S. Evaluation of the Birmingham IBS symptom questionnaire. BMC Gastroenterol 2008; 8: 30–30.
    1. Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci 1998; 43: 400–11.
    1. Drossman DA, Patrick DL, Whitehead WE, Toner BB, Diamant NE, Hu Y, Jia H, Bangdiwala SI. Further validation of the IBS-QOL: a disease-specific quality-of-life questionnaire. Am J Gastroenterol 2000; 95: 999–1007.
    1. Talley NJ, Verlinden M, Jones M. Quality of life in functional dyspepsia: responsiveness of the Nepean Dyspepsia Index and development of a new 10-item short form. Aliment Pharmacol Ther 2001; 15: 207–16.
    1. Arslan G, Lind R, Olafsson S, Florvaag E, Berstad A. Quality of life in patients with subjective food hypersensitivity: applicability of the 10-item short form of the Nepean Dyspepsia Index. Dig Dis Sci 2004; 49: 680–7.
    1. Meltzer HM, Brantsaeter AL, Ydersbond TA, Alexander J, Haugen M. Methodological challenges when monitoring the diet of pregnant women in a large study: experiences from the Norwegian Mother and Child Cohort Study (MoBa). Matern Child Nutr 2008; 4: 14–27.
    1. Rimestad AH, Borgejordet A, Vesterhus KN, Sygnestveit K, Løken EB, Trygg K. Matvaretabellen [The Norwegian Food Composition Table]. Oslo: Norwegian Food Safety Authority.
    1. Masson LF, McNeill G, Tomany JO, Simpson JA, Peace HS, Wei L, Grubb DA, Bolton-Smith C. Statistical approaches for assessing the relative validity of a food-frequency questionnaire: use of correlation coefficients and the kappa statistic. Public Health Nutr 2003; 6: 313–21.
    1. Brantsaeter AL, Haugen M, Alexander J, Meltzer HM. Validity of a new food frequency questionnaire for pregnant women in the Norwegian mother and child cohort study (MoBa). Matern Child Nutr 2008; 4: 28–43.
    1. El-Salhy M, Hatlebakk JG, Hausken T. Reduction in duodenal endocrine cells in irritable bowel syndrome is associated with stem cell abnormalities. World J Gastroenterol 2015; 21: 9577–87.
    1. Enck P, Klosterhalfen S, Kruis W. [Determination of placebo effect in irritable bowel syndrome]. Dtsch Med Wochenschr 2005; 130: 1934–7.
    1. Abdul-Baki H, El H, II, Elzahabi L, Azar C, Aoun E, Skoury A, Chaar H, Sharara AI. A randomized controlled trial of imipramine in patients with irritable bowel syndrome. World J Gastroenterol 2009; 15: 3636–42.
    1. Zernicke KA, Campbell TS, Blustein PK, Fung TS, Johnson JA, Bacon SL, Carlson LE. Mindfulness-based stress reduction for the treatment of irritable bowel syndrome symptoms: a randomized wait-list controlled trial. Int J Behav Med 2013; 20: 385–96.
    1. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 2014; 146: 67–75.e65.
    1. Sandstrom O, El-Salhy M. Ageing and endocrine cells of human duodenum. Mech Ageing Dev 1999; 108: 39–48.
    1. Lam IP, Siu FK, Chu JY, Chow BK. Multiple actions of secretin in the human body. Int Rev Cytol 2008; 265: 159–90.
    1. Chu JY, Cheng CY, Lee VH, Chan YS, Chow BK. Secretin and body fluid homeostasis. Kidney Int 2011; 79: 280–7.
    1. Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK. Secretin as a neurohypophysial factor regulating body water homeostasis. Proc Natl Acad Sci USA 2009; 106: 15961–6.
    1. Lu Y, Owyang C. Secretin-induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways. Neurogastroenterol Motil 2009; 21: 754–e47..
    1. Murthy SN, Ganiban G. Effect of the secretin family of peptides on gastric emptying and small intestinal transit in rats. Peptides 1988; 9: 583–8.
    1. Moran TH, McHugh PR. Cholecystokinin suppresses food intake by inhibiting gastric emptying. Am J Physiol 1982; 242: R491–7.
    1. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA. Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest 1985; 75: 1144–52.
    1. Suzuki S, Takiguchi S, Sato N, Kanai S, Kawanami T, Yoshida Y, Miyasaka K, Takata Y, Funakoshi A, Noda T. Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion: a study in CCK-A receptor knockout mice. Jpn J Physiol 2001; 51: 585–90.
    1. Reidelberger RD, Solomon TE. Comparative effects of CCK-8 on feeding, sham feeding, and exocrine pancreatic secretion in rats. Am J Physiol 1986; 251: R97–105.
    1. Reidelberger RD, Varga G, Liehr RM, Castellanos DA, Rosenquist GL, Wong HC, Walsh JH. Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats. Am J Physiol 1994; 267: R901–8.
    1. Efendic S, Portwood N. Overview of incretin hormones. Horm Metab Res 2004; 36: 742–6.
    1. Villar HV, Fender HR, Rayford PL, Bloom SR, Ramus NI, Thompson JC. Suppression of gastrin release and gastric secretion by gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP). Ann Surg 1976; 184: 97–102.
    1. Pederson RA, Brown JC. Inhibition of histamine-, pentagastrin-, and insulin-stimulated canine gastric secretion by pure “gastric inhibitory polypeptide”. Gastroenterology 1972; 62: 393–400.
    1. Gershon MD. Plasticity in serotonin control mechanisms in the gut. Curr Opin Pharmacol 2003; 3: 600–7.
    1. Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 2013; 20: 14–21.
    1. Michel K, Sann H, Schaaf C, Schemann M. Subpopulations of gastric myenteric neurons are differentially activated via distinct serotonin receptors: projection, neurochemical coding, and functional implications. J Neurosci 1997; 17: 8009–17.
    1. Gershon MD, Wade PR, Kirchgessner AL, Tamir H. 5-HT receptor subtypes outside the central nervous system. Roles in the physiology of the gut. Neuropsychopharmacology 1990; 3: 385–95.
    1. El-Salhy M, Gilja OH, Gundersen D, Hatlebakk JG, Hausken T. Interaction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (review). Int J Mol Med 2014; 34: 363–71.
    1. Boden G, Sivitz MC, Owen OE, Essa-Koumar N, Landor JH. Somatostatin suppresses secretin and pancreatic exocrine secretion. Science 1975; 190: 163–5.
    1. Konturek SJ, Konturek JW, Lamers CB, Tasler J, Bilski J. Role of secretin and CCK in the stimulation of pancreatic secretion in conscious dogs. Effects of atropine and somatostatin. Int J Pancreatol 1987; 2: 223–35.
    1. Wiener I, Inoue K, Fagan CJ, Lilja P, Watson LC, Thompson JC. Release of cholecystokinin in man: correlation of blood levels with gallbladder contraction. Ann Surg 1981; 194: 321–7.
    1. Shibue K, Yamane S, Harada N, Hamasaki A, Suzuki K, Joo E, Iwasaki K, Nasteska D, Harada T, Hayashi Y, Adachi Y, Owada Y, Takayanagi R, Inagaki N. Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion. Am J Physiol Endocrinol Metab 2015; 308: E583–91.
    1. Yamane S, Harada N, Hamasaki A, Muraoka A, Joo E, Suzuki K, Nasteska D, Tanaka D, Ogura M, Harashima S, Inagaki N. Effects of glucose and meal ingestion on incretin secretion in Japanese subjects with normal glucose tolerance. J Diabetes Investig 2012; 3: 80–5.
    1. El-Salhy M, Hatlebakk JG, Gilja OH, Hausken T. Irritable bowel syndrome: recent developments in diagnosis, pathophysiology, and treatment. Expert Rev Gastroenterol Hepatol 2014; 8: 435–43.
    1. Hocker M, Wiedenmann B. Molecular mechanisms of enteroendocrine differentiation. Ann NY Acad Sci 1998; 859: 160–74.
    1. Inokuchi H, Fujimoto S, Kawai K. Cellular kinetics of gastrointestinal mucosa, with special reference to gut endocrine cells. Arch Histol Jpn 1983; 46: 137–57.

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