Expression of the fructose transporter GLUT5 in patients with fructose malabsorption

Abstract

Background Patients with abdominal symptoms are frequently diagnosed with fructose malabsorption (FM). Fructose is absorbed by monosaccharide transporters located in the brush border of the human small intestine. The aim of this study was to investigate the histoanatomical distribution of the main fructose transporter GLUT5.

Materials and methods We studied 223 patients diagnosed with FM by a hydrogen breath test and grouped according to their response to a fructose-free diet. The control group were 42 healthy individuals and 29 patients with celiac disease (CD). The fructose breath test was done with 50 g fructose. The expression of Glut5 in duodenal biopsy specimens was studied by immunohistochemistry. The Kruskal-Wallis-test and Mann-Whitney U-test were used to carry out the statistical analysis.

Results The histoanatomical expression pattern of GLUT5 did not differ significantly between those patients with FM who responded completely to a fructose-free diet (n = 183) and healthy individuals (n = 42); nor did it correlate to H2 production measured in fructose breath testing. In patients with FM, the GLUT5 expression pattern did not differ between those individuals responding to a fructose-free diet and those who did not. However, GLUT5 expression pattern was significantly different in patients with CD (n = 29) compared to patients with FM and to healthy individuals (p = 0.009).

Conclusion GLUT5 expression patterns are not be related to adult patients with FM. However, in secondary malabsorption, a decreased GLUT5 expression was found. Further investigation is needed to understand the essential factors in FM and the influence on functional gastrointestinal disorders.

Zusammenfassung

Fruktose wird durch den GLUT5-Rezeptor resorbiert, die Frage der klinischen Bedeutung bei der Fruktosemalabsorption ist ungeklärt. Daher haben wir insgesamt 223 Patienten mit einer Fruktosemalabsorption mit Normalkontrollen und Zöliakiepatienten verglichen. Nach H2-Atemtestung wurde die Diagnose der Fruktosemalabsorption durch die Besserung der klinischen Beschwerden nach Fruktoserestriktion verifiziert. Die Expression des GLUT5-Rezeptors in der Dünndarmbiopsie wurde mit Zöliakiepatienten und Normalkontrollen verglichen. Es zeigt sich keine verminderte GLUT5-Expression bei Patienten mit einer Fruktosemalabsorption im Vergleich zu Normalkontrollen. Hingegen ist bei der Zöliakie eine entzündungsabhängige Konzentrationsänderung von GLUT5 zu verzeichnen. Diese Daten belegen, dass die klinische Bedeutung der Fruktosemalabsorption nicht von der Rezeptorverteilung von GLUT5 abhängig sind und daher die Bestimmung desselben nicht zur Diagnostik geeignet ist.

Key words

malabsorption - colon irritabile - fructose malabsorption

Schlüsselwörter

Malabsorption - Reizdarmsyndrom - Fruktosemalabsorption

^* Shared senior authorship.

Publikationsverlauf

Eingereicht: 15. September 2019

Angenommen: 05. April 2020

Artikel online veröffentlicht:
15. Juni 2021

• References

• 1 Simrén M, Månsson A, Langkilde AM. et al. Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 2001; 63: 108-115
• 2 Böhn L, Störsrud S, Törnblom H. et al. Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 2013; 108: 634-641
• 3 Gibson PR, Newnham E, Barrett JS. et al. Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 2006; 25: 349-363
• 4 Barrett JS, Gearry RB, Muir JG. et al. Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon. Aliment Pharmacol Ther 2010; 31: 874-882
• 5 Ong DK, Mitchell SB, Barrett JS. et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol 2010; 25: 1366-1373
• 6 Melchior C, Gourcerol G, Dechelotte P. et al. Symptomatic fructose malabsorption in irritable bowel syndrome: a prospective study. United Eur Gastroenterol J 2014; 2: 131-137
• 7 Choi YK, Johlin FC, Summers RW. et al. Fructose intolerance: an under-recognized problem. Am J Gastroenterol 2003; 98: 1348-1353
• 8 Marriott BP, Cole N, Lee E. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J Nutr 2009; 139: 1228S-1235S
• 9 USDA ERS. Sugar and sweeteners yearbook tables [Internet]. [cited 2017 Mar 4]. Available from: http://www.ers.usda.gov/data-products/sugar-and-sweeteners-yearbook-tables/sugar-and-sweeteners-yearbook-tables/#U.S.%20Consumption%20of%20Caloric%20Sweeteners
• 10 Wasserman D, Hoekstra JH, Tolia V. et al. Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption. J Clin Invest 1996; 98: 2398-2402
• 11 Kellett GL, Brot-Laroche E, Mace OJ. et al. Sugar absorption in the intestine: the role of GLUT2. Annu Rev Nutr 2008; 28: 35-54
• 12 Barone S, Fussell SL, Singh AK. et al. Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J Biol Chem 2009; 284: 5056-5066
• 13 Gorboulev V, Schürmann A, Vallon V. et al. Na+-d-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 2012; 61: 187-196
• 14 Röder PV, Geillinger KE, Zietek TS. et al. The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS ONE 2014; 9: e89977
• 15 Castello A, Guma A, Sevilla L. et al. Regulation of GLUT5 gene expression in rat intestinal mucosa: regional distribution, circadian rhythm, perinatal development and effect of diabetes. Biochem J 1995; 309: 271-277
• 16 Jiang L, David ES, Espina N. et al. GLUT-5 expression in neonatal rats: crypt-villus location and age-dependent regulation. Am J Physiol-Gastrointest Liver Physiol 2001; 281: G666-G674
• 17 Duro D, Rising R, Cedillo M. et al. Association between infantile colic and carbohydrate malabsorption from fruit juices in infancy. Pediatrics 2002; 109: 797-805
• 18 Jones HF, Burt E, Dowling K. et al. Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 2011; 52: 581-584
• 19 Wilder-Smith CH, Li X, Ho SS. et al. Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance. United Eur Gastroenterol J 2014; 2: 14-21
• 20 Felber J, Aust D, Baas S. et al. Results of a S2k-consensus conference of the German Society of Gastroenterolgy, Digestive, and Metabolic Diseases (DGVS) in conjunction with the German Coeliac Society (DZG) regarding coeliac disease, wheat allergy, and wheat sensitivity. Z Gastroenterol 2014; 52: 711-743
• 21 Davidson NO, Hausman AM, Ifkovits CA. et al. Human intestinal glucose transporter expression and localization of GLUT5. Am J Physiol 1992; 262: C795-C800
• 22 Ferraris RP. Dietary and developmental regulation of intestinal sugar transport. Biochem J 2001; 360: 265-276
• 23 Truswell AS, Seach JM, Thorburn AW. Incomplete absorption of pure fructose in healthy subjects and the facilitating effect of glucose. Am J Clin Nutr 1988; 48: 1424-1430
• 24 Rao SS, Attaluri A, Anderson L. et al. Stumbo P. The ability of the normal human small intestine to absorb fructose: evaluation by breath testing. Clin Gastroenterol Hepatol 2007; 5: 959-963
• 25 Fernández-Bañares F, Rosinach M, Esteve M. et al. Sugar malabsorption in functional abdominal bloating: a pilot study on the long-term effect of dietary treatment. Clin Nutr Edinb Scotl 2006; 25: 824-831
• 26 Goldstein R, Braverman D, Stankiewicz H. Carbohydrate malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints. Isr Med Assoc J IMAJ 2000; 2: 583-587
• 27 Kayano T, Burant CF, Fukumoto H. et al. Human facilitative glucose transporters. Isolation, functional characterization, and gene localization of cDNAs encoding an isoform (GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue and an unusual glucose transporter pseudogene-like sequence (GLUT6). J Biol Chem 1990; 265: 13276-13282
• 28 Burant CF, Takeda J, Brot-Laroche E. et al. Fructose transporter in human spermatozoa and small intestine is GLUT5. J Biol Chem 1992; 267: 14523-14526
• 29 Mantych GJ, James DE, Devaskar SU. Jejunal/kidney glucose transporter isoform (Glut-5) is expressed in the human blood-brain barrier. Endocrinology 1993; 132: 35-40
• 30 Mahraoui L, Rousset M, Dussaulx E. et al. Expression and localization of GLUT-5 in Caco-2 cells, human small intestine, and colon. Am J Physiol 1992; 263: G312-G318
• 31 Gouyon F, Caillaud L, Carrière V. et al. Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: a study in GLUT2-null mice. J Physiol 2003; 552: 823-832
• 32 Douard V, Ferraris RP. The role of fructose transporters in diseases linked to excessive fructose intake. J Physiol 2013; 591: 401-414
• 33 Kyaw MH, Mayberry JF. Fructose malabsorption: true condition or a variance from normality. J Clin Gastroenterol 2011; 45: 16-21
• 34 Jung KW, Seo M, Cho YH. et al. Prevalence of fructose malabsorption in patients with irritable bowel syndrome after excluding small intestinal bacterial overgrowth. J Neurogastroenterol Motil 2018; 24: 307-316
• 35 Shepherd SJ, Parker FC, Muir JG. et al. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol 2008; 6: 765-771
• 36 de Roest RH, Dobbs BR, Chapman BA. et al. The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study. Int J Clin Pract 2013; 67: 895-903
• 37 Piche T, Barbara G, Aubert P. et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009; 58: 196-201
• 38 Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain 2009; 146: 41-46
• 39 Manabe N, Wong BS, Camilleri M. et al. Lower functional gastrointestinal disorders: evidence of abnormal colonic transit in a 287 patient cohort. Neurogastroenterol Motil 2010; 22: 293–e82
• 40 Neal KR, Barker L, Spiller RC. Prognosis in post-infective irritable bowel syndrome: a six year follow up study. Gut 2002; 51: 410-413
• 41 Chadwick VS, Chen W, Shu D. et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002; 122: 1778-1783
• 42 Tana C, Umesaki Y, Imaoka A. et al. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 2010; 22: 512-519
• 43 Mazur M, Furgała A, Jabłoński K. et al. Dysfunction of the autonomic nervous system activity is responsible for gastric myoelectric disturbances in the irritable bowel syndrome patients. J Physiol Pharmacol Off J Pol Physiol Soc 2007; 58 (Suppl. 03) 131-139
• 44 Spaziani R, Bayati A, Redmond K. et al. Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and baroreceptor sensitivity. Neurogastroenterol Motil 2008; 20: 336-342