Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Bariatric Surgery

Intestinal barrier function in morbid obesity: results of a prospective study on the effect of sleeve gastrectomy

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

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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.

  2. 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.

    Article  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. 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.

    Article  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. 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.

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. Michielan A, D’Inca R. Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of leaky gut. Mediators Inflamm. 2015;2015:628157.

    Article  Google Scholar 

  18. Teshima CW, Dieleman LA, Meddings JB. Abnormal intestinal permeability in Crohn’s disease pathogenesis. Ann N Y Acad Sci. 2012;1258:159–65.

    Article  CAS  Google Scholar 

  19. 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.

  20. 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.

    Article  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. 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.

    Article  CAS  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. 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.

    CAS  PubMed  Google Scholar 

  28. 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.

    Article  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. 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.

    Article  CAS  Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. 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.

    CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  Google Scholar 

  34. 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.

    Article  CAS  Google Scholar 

  35. 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.

    Article  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Jennifer Wilbrink.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-019-0492-z

This article is cited by

Search

Quick links