Abstract
Background
Obesity has been associated with impaired intestinal barrier function. It is not known whether bariatric surgery leads to changes in intestinal barrier function. We hypothesized that obesity is associated with disturbances in gastrointestinal barrier function, and that after bariatric surgery barrier function will improve.
Methods
Prospective single center study in which we assessed segmental gut permeability by urinary recovery of a multisugar drink in 27 morbidly obese (BMI 43.3 ± 1.1 kg/m2) and 27 age and gender matched lean subjects (BMI 22.9 ± 0.43 kg/m2). Fecal calprotectin, SCFAs, plasma cytokines, and hsCRP were assessed as inflammatory and metabolic markers. Comparisons: (a) morbidly obese subjects vs. controls and (b) 2 and 6 months postsleeve vs. presleeve gastrectomy (n = 14). In another group of 10 morbidly obese and 11 matched lean subjects colonic and ileal biopsies were obtained in order to measure gene transcription of tight junction proteins.
Results
Gastroduodenal permeability (urinary sucrose recovery) was significantly increased in obese vs. lean controls (p < 0.05). Small intestinal and colonic permeability (urinary recovery of lactulose/L-rhamnose and sucralose/erythritol, respectively) in obese subjects were not significantly different from controls. Morbidly obese subjects had a proinflammatory systemic and intestinal profile compared with lean subjects. After sleeve gastrectomy BMI decreased significantly (p < 0.001). Postsleeve gastroduodenal permeability normalized to values that do not differ from lean controls.
Conclusions
Gastroduodenal permeability, but not small intestinal or colonic permeability, is significantly increased in morbidly obese patients. After sleeve gastrectomy, gastroduodenal permeability normalized to values in the range of lean controls. Thus, the proximal gastrointestinal barrier is compromised in morbid obesity and is associated with a proinflammatory intestinal and systemic profile.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pekkarinen T, Mustonen H, Sane T, Jaser N, Juuti A, Leivonen M. Long-term effect of gastric bypass and sleeve gastrectomy on severe obesity: do preoperative weight loss and binge eating behavior predict the outcome of bariatric surgery? Obes Surg. 2016;26:2161–7.
Arismendi E, Rivas E, Agusti A, Rios J, Barreiro E, Vidal J, et al. The systemic inflammome of severe obesity before and after bariatric surgery. PLoS ONE. 2014;9:e107859.
Damms-Machado A, Louis S, Schnitzer A, Volynets V, Rings A, Basrai M, et al. Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction. Am J Clin Nutr. 2017;105:127–35.
Genser L, Aguanno D, Soula HA, Dong L, Trystram L, Assmann K, et al. Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes. J Pathol. 2018;246:217–30.
Rainone V, Schneider L, Saulle I, Ricci C, Biasin M, Al-Daghri NM, et al. Upregulation of inflammasome activity and increased gut permeability are associated with obesity in children and adolescents. Int J Obes. 2016;40:1026–33.
Busetto L, Dixon J, De Luca M, Shikora S, Pories W, Angrisani L. Bariatric surgery in class I obesity: a position statement from the international federation for the surgery of obesity and metabolic disorders (IFSO). Obes Surg. 2014;24:487–519.
van Wijck K, Verlinden TJ, van Eijk HM, Dekker J, Buurman WA, Dejong CH, et al. Novel multi-sugar assay for site-specific gastrointestinal permeability analysis: a randomized controlled crossover trial. Clin Nutr. 2013;32:245–51.
Verdam FJ, Greve JW, Roosta S, van Eijk H, Bouvy N, Buurman WA, et al. Small intestinal alterations in severely obese hyperglycemic subjects. J Clin Endocrinol Metab. 2011;96:E379–83.
Mujagic Z, Jonkers D, Ludidi S, Keszthelyi D, Hesselink MA, Weerts Z et al. Biomarkers for visceral hypersensitivity in patients with irritable bowel syndrome. Neurogastroenterol Motil 2017;29:e13137.
Verbeke KA, Boobis AR, Chiodini A, Edwards CA, Franck A, Kleerebezem M, et al. Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutr Res Rev. 2015;28:42–66.
Pijls KE, Jonkers DM, Elizalde M, Drittij-Reijnders MJ, Haenen GR, Bast A, et al. Is intestinal oxidative stress involved in patients with compensated liver cirrhosis? Ann Hepatol. 2016;15:402–9.
Keszthelyi D, Troost FJ, Jonkers DM, van Donkelaar EL, Dekker J, Buurman WA, et al. Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine? Am J Clin Nutr. 2012;95:603–8.
Troost FJ, Saris WH, Brummer RJ. Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers. Eur J Clin Nutr. 2003;57:1579–85.
Brignardello J, Morales P, Diaz E, Romero J, Brunser O, Gotteland M. Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function. Aliment Pharmacol Ther. 2010;32:1307–14.
Carswell KA, Vincent RP, Belgaumkar AP, Sherwood RA, Amiel SA, Patel AG, et al. The effect of bariatric surgery on intestinal absorption and transit time. Obes Surg. 2014;24:796–805.
Chang J, Leong RW, Wasinger VC, Ip M, Yang M, Phan TG. Impaired intestinal permeability contributes to ongoing bowel symptoms in patients with inflammatory bowel disease and mucosal healing. Gastroenterology. 2017;153:723–31 e1.
Michielan A, D’Inca R. Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of leaky gut. Mediators Inflamm. 2015;2015:628157.
Teshima CW, Dieleman LA, Meddings JB. Abnormal intestinal permeability in Crohn’s disease pathogenesis. Ann N Y Acad Sci. 2012;1258:159–65.
McCarty TR, Jirapinyo P, Thompson CC. Effect of sleeve gastrectomy on ghrelin, GLP-1, PYY, and GIP gut hormones: a systematic review and meta-analysis. Ann Surg. 2019.
Savassi-Rocha AL, Diniz MT, Vilela EG, Diniz Mde F, Sanches SR, da Cunha AS, et al. Changes in intestinal permeability after Roux-en-Y gastric bypass. Obes Surg. 2014;24:184–90.
Trung VN, Yamamoto H, Furukawa A, Yamaguchi T, Murata S, Yoshimura M, et al. Enhanced intestinal motility during oral glucose tolerance test after laparoscopic sleeve gastrectomy: preliminary results using cine magnetic resonance imaging. PLoS ONE. 2013;8:e65739.
Melissas J, Leventi A, Klinaki I, Perisinakis K, Koukouraki S, de Bree E, et al. Alterations of global gastrointestinal motility after sleeve gastrectomy: a prospective study. Ann Surg. 2013;258:976–82.
Mans E, Serra-Prat M, Palomera E, Sunol X, Clave P. Sleeve gastrectomy effects on hunger, satiation, and gastrointestinal hormone and motility responses after a liquid meal test. Am J Clin Nutr. 2015;102:540–7.
Madsen JL, Scharff O, Rabol A, Krogsgaard OW. Relationship between small-intestinal transit rate and intestinal absorption of (14)C-labelled mannitol and (51)Cr-labelled ethylenediaminetetraacetic acid in healthy subjects. Scand J Gastroenterol. 1996;31:254–9.
Little TJ, Cvijanovic N, DiPatrizio NV, Argueta DA, Rayner CK, Feinle-Bisset C, et al. Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion. Am J Physiol Endocrinol Metab. 2018;315:E489–95.
Dimitriadis E, Daskalakis M, Kampa M, Peppe A, Papadakis JA, Melissas J. Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study. Ann Surg. 2013;257:647–54.
Rojano-Rodriguez ME, Valenzuela-Salazar C, Cardenas-Lailson LE, Romero Loera LS, Torres-Olalde M, Moreno-Portillo M. C-reactive protein level in morbidly obese patients before and after bariatric surgery. Rev Gastroenterol Mex. 2014;79:90–5.
Illan-Gomez F, Gonzalvez-Ortega M, Orea-Soler I, Alcaraz-Tafalla MS, Aragon-Alonso A, Pascual-Diaz M, et al. Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg. 2012;22:950–5.
Poullis A, Foster R, Shetty A, Fagerhol MK, Mendall MA. Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2004;13:279–84.
Verdam FJ, Fuentes S, de Jonge C, Zoetendal EG, Erbil R, Greve JW, et al. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity. 2013;21:E607–15.
Kant P, Fazakerley R, Hull MA. Faecal calprotectin levels before and after weight loss in obese and overweight subjects. Int J Obes. 2013;37:317–9.
Park HK, Sinar DR, Sloss RR, Whitley TW, Silverman JF. Histologic and endoscopic studies before and after gastric bypass surgery. Arch Pathol Lab Med. 1986;110:1164–7.
Sinar DR, Flickinger EG, Park HK, Sloss RR. Retrograde endoscopy of the bypassed stomach segment after gastric bypass surgery: unexpected lesions. South Med J. 1985;78:255–8.
Rahat-Rozenbloom S, Fernandes J, Gloor GB, Wolever TM. Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes. 2014;38:1525–31.
Takashina C, Tsujino I, Watanabe T, Sakaue S, Ikeda D, Yamada A, et al. Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance. Nutr Metab (Lond). 2016;13:5.
Acknowledgements
We would like to thank Anton van der Stokker, analyst at the laboratory of the Catharina hospital in Eindhoven, for analyzing hsCRP and for collecting and preserving all specimens before analysis. We would like to thank the department of Surgery in Maastricht for analyzing urine specimens.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Wilbrink, J., Bernards, N., Mujagic, Z. et al. Intestinal barrier function in morbid obesity: results of a prospective study on the effect of sleeve gastrectomy. Int J Obes 44, 368–376 (2020). https://doi.org/10.1038/s41366-019-0492-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41366-019-0492-z
This article is cited by
-
Paracellular permeability and tight junction regulation in gut health and disease
Nature Reviews Gastroenterology & Hepatology (2023)
-
Serum Versus Fecal Calprotectin Levels in Patients with Severe Obesity Before and 6 Months After Roux-Y-Gastric Bypass: Report of the Prospective Leaky-Gut Study
Obesity Surgery (2023)