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Impact of Laparoscopic Sleeve Gastrectomy on Gut Permeability in Morbidly Obese Subjects

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A Correction to this article was published on 29 April 2021

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Abstract

Background

Recent studies have suggested that obesity is associated with an increased intestinal permeability as well as an altered microbiota profile. These conditions can promote the translocation of lipopolysaccharide into the circulation and, subsequently, contribute to the observed systemic inflammation. Our aim was to assess gut permeability in patients with obesity compared to non-obese subjects as well as after excessive weight loss following laparoscopic sleeve gastrectomy (LSG).

Methods

We analyzed the dietary intake, metabolic and inflammatory markers, gut permeability (four-probe sugar test), and microbiota composition in 17 morbidly obese patients before and after LSG as well as in 17 age- and gender-matched non-obese subjects. Additionally, we compared gut permeability and inflammatory markers in patients of different stages of obesity.

Results

Patients with obesity showed elevated levels of C-reactive protein and lipopolysaccharide-binding protein as compared to non-obese subjects, but no differences were noted for gut permeability between these two groups. LSG led to improvements in metabolic and inflammatory parameters in the obese patients. Moreover, gastroduodenal as well as small intestinal permeability decreased, whereas colonic permeability increased after surgery. Regarding gut microbiota, differences were noted for main phyla and alpha-diversity between non-obese and obese subjects. After surgery, the composition of the microbiota showed a tendency toward the pattern of the non-obese group.

Conclusions

Gut permeability is not dependent on body mass index, whereas weight loss after LSG initiates distinct changes in gastroduodenal, intestinal, and colonic permeability. These changes do not seem to be associated with changes in the microbiota composition.

Clinical Trial Registry Number and Website

The trials were registered at https://www.drks.de/drks_web/ with the number DRKS00009008 and DRKS00006210.

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References

  1. Han TS, Lean ME. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease. JRSM Cardiovasc Dis. 2016;5:1–13. https://doi.org/10.1177/2048004016633371.

    Article  Google Scholar 

  2. Nguyen NT, Varela JE. Bariatric surgery for obesity and metabolic disorders: state of the art. Nat Rev Gastroenterol Hepatol. 2017;14:160–9. https://doi.org/10.1038/nrgastro.2016.170.

    Article  PubMed  Google Scholar 

  3. Cani PD, Neyrinck AM, Fava F, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–83. https://doi.org/10.1007/s00125-007-0791-0.

    Article  CAS  PubMed  Google Scholar 

  4. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81. https://doi.org/10.2337/db07-1403.

    Article  CAS  PubMed  Google Scholar 

  5. Lam YY, Ha CWY, Campbell CR, et al. Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS One. 2012;7:e34233. https://doi.org/10.1371/journal.pone.0034233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72. https://doi.org/10.2337/db06-1491.

    Article  CAS  PubMed  Google Scholar 

  7. Verdam FJ, Fuentes S, de JC, et al. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring). 2013;21:E607–15. https://doi.org/10.1002/oby.20466.

    Article  CAS  Google Scholar 

  8. Teixeira TFS, Souza NCS, Chiarello PG, et al. Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors. Clin Nutr. 2012;31:735–40. https://doi.org/10.1016/j.clnu.2012.02.009.

    Article  CAS  PubMed  Google Scholar 

  9. Gummesson A, Carlsson LMS, Storlien LH, et al. Intestinal permeability is associated with visceral adiposity in healthy women. Obesity (Silver Spring). 2011;19:2280–2. https://doi.org/10.1038/oby.2011.251.

    Article  Google Scholar 

  10. Brignardello J, Morales P, Diaz E, et al. 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. https://doi.org/10.1111/j.1365-2036.2010.04475.x.

    Article  CAS  PubMed  Google Scholar 

  11. Savassi-Rocha AL, Diniz MTC, Vilela EG, et al. Changes in intestinal permeability after Roux-en-Y gastric bypass. Obes Surg. 2014;24:184–90. https://doi.org/10.1007/s11695-013-1084-y.

    Article  PubMed  Google Scholar 

  12. Blanchard C, Moreau F, Chevalier J, et al. Sleeve gastrectomy alters intestinal permeability in diet-induced obese mice. Obes Surg. 2017;27:2590–8. https://doi.org/10.1007/s11695-017-2670-1.

    Article  PubMed  Google Scholar 

  13. Ott B, Skurk T, Hastreiter L, et al. Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women. Sci Rep. 2017;7:11955. https://doi.org/10.1038/s41598-017-12109-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  15. Norman K, Pirlich M, Schulzke J-D, et al. Increased intestinal permeability in malnourished patients with liver cirrhosis. Eur J Clin Nutr. 2012;66:1116–9. https://doi.org/10.1038/ejcn.2012.104.

    Article  CAS  PubMed  Google Scholar 

  16. Lagkouvardos I, Kläring K, Heinzmann SS, et al. Gut metabolites and bacterial community networks during a pilot intervention study with flaxseeds in healthy adult men. Mol Nutr Food Res. 2015;59:1614–28. https://doi.org/10.1002/mnfr.201500125.

    Article  CAS  PubMed  Google Scholar 

  17. Lagkouvardos I, Joseph D, Kapfhammer M, et al. IMNGS: a comprehensive open resource of processed 16S rRNA microbial profiles for ecology and diversity studies. Sci Rep. 2016;6:33721. https://doi.org/10.1038/srep33721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10:996–8. https://doi.org/10.1038/nmeth.2604.

    Article  CAS  PubMed  Google Scholar 

  19. Jackson MA, Goodrich JK, Maxan M-E, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749–56. https://doi.org/10.1136/gutjnl-2015-310861.

    Article  CAS  PubMed  Google Scholar 

  20. Imhann F, Bonder MJ, Vila AV, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–8. https://doi.org/10.1136/gutjnl-2015-310376.

    Article  CAS  PubMed  Google Scholar 

  21. Hoogerboord M, Wiebe S, Klassen D, et al. Laparoscopic sleeve gastrectomy: perioperative outcomes, weight loss and impact on type 2 diabetes mellitus over 2 years. Can J Surg. 2014;57:101–5.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Roa PE, Kaidar-Person O, Pinto D, et al. Laparoscopic sleeve gastrectomy as treatment for morbid besity: technique and short-term outcome. Obes Surg. 2006;16:1323–6.

    Article  PubMed  Google Scholar 

  23. Fasano A, Fiorentini C, Donelli G, et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest. 1995;96:710–20. https://doi.org/10.1172/JCI118114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Teixeira TFS, Collado MC, Ferreira CLLF, et al. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res. 2012;32:637–47. https://doi.org/10.1016/j.nutres.2012.07.003.

    Article  CAS  PubMed  Google Scholar 

  25. Scheffler L, Crane A, Heyne H, et al. Widely used commercial ELISA does not detect precursor of haptoglobin2, but recognizes properdin as a potential second member of the zonulin family. Front Endocrinol (Lausanne). 2018;9:22. https://doi.org/10.3389/fendo.2018.00022.

    Article  Google Scholar 

  26. Shah S, Shah P, Todkar J, et al. Prospective controlled study of effect of laparoscopic sleeve gastrectomy on small bowel transit time and gastric emptying half-time in morbidly obese patients with type 2 diabetes mellitus. Surg Obes Relat Dis. 2010;6:152–7. https://doi.org/10.1016/j.soard.2009.11.019.

    Article  PubMed  Google Scholar 

  27. Tuomi K, Logomarsino JV. Bacterial lipopolysaccharide, lipopolysaccharide-binding protein, and other inflammatory markers in obesity and after bariatric surgery. Metab Syndr Relat Disord. 2016;14:279–88. https://doi.org/10.1089/met.2015.0170.

    Article  CAS  PubMed  Google Scholar 

  28. van Dielen FMH, Buurman WA, Hadfoune M, et al. Macrophage inhibitory factor, plasminogen activator inhibitor-1, other acute phase proteins, and inflammatory mediators normalize as a result of weight loss in morbidly obese subjects treated with gastric restrictive surgery. J Clin Endocrinol Metab. 2004;89:4062–8. https://doi.org/10.1210/jc.2003-032125.

    Article  CAS  PubMed  Google Scholar 

  29. Moschen AR, Molnar C, Geiger S, et al. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut. 2010;59:1259–64. https://doi.org/10.1136/gut.2010.214577.

    Article  CAS  PubMed  Google Scholar 

  30. Skurk T, Alberti-Huber C, Herder C, et al. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92:1023–33. https://doi.org/10.1210/jc.2006-1055.

    Article  CAS  PubMed  Google Scholar 

  31. Damms-Machado A, Louis S, Schnitzer A, 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. https://doi.org/10.3945/ajcn.116.131110.

    Article  CAS  PubMed  Google Scholar 

  32. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4. https://doi.org/10.1038/nature07540.

    Article  CAS  PubMed  Google Scholar 

  33. Ley RE, Bäckhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102:11070–5. https://doi.org/10.1073/pnas.0504978102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174–80. https://doi.org/10.1038/nature09944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Costea PI, Hildebrand F, Arumugam M, et al. Enterotypes in the landscape of gut microbial community composition. Nat Microbiol. 2018;3:8–16. https://doi.org/10.1038/s41564-017-0072-8.

    Article  CAS  PubMed  Google Scholar 

  36. Murphy R, Tsai P, Jüllig M, et al. Differential changes in gut microbiota after gastric bypass and sleeve gastrectomy bariatric surgery vary according to diabetes remission. Obes Surg. 2017;27:917–25. https://doi.org/10.1007/s11695-016-2399-2.

    Article  PubMed  Google Scholar 

  37. Damms-Machado A, Mitra S, Schollenberger AE, et al. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int. 2015;2015:806248–12. https://doi.org/10.1155/2015/806248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tremaroli V, Karlsson F, Werling M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228–38. https://doi.org/10.1016/j.cmet.2015.07.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Patil DP, Dhotre DP, Chavan SG, et al. Molecular analysis of gut microbiota in obesity among Indian individuals. J Biosci. 2012;37:647–57. https://doi.org/10.1007/s12038-012-9244-0.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We highly acknowledge Prof. Dr. Thomas Hüttl, Dr. Peter Stauch, Dr. Otto Dietl, and Hildegard Wood together with their whole team at the Adipositas Zentrum München Bogenhausen; Dr. Georg Dechantsreiter and team at the Krankenhaus Landshut Achdorf; and Dr. Andreas Limberger and team at the Kreiskrankenhaus Schrobenhausen for their support in recruitment and sample collection. Additionally, we are thankful to Martina Werich for the analysis of sugars in the urine samples. We are grateful to Manuela Hubersberger for her excellent technical assistance and to the ZIEL Core Facility Microbiome/NGS at the TU Munich for support with high-throughput 16S rRNA gene amplicon sequencing and analysis.

Funding

The study was founded by the DFG (Deutsche Forschungsgemeinschaft) as part of the Graduiertenkolleg 1482 as well as by the BMBF (Federal Ministry of Education and Research, grant no. 0315674) and in part by the Else Kröner-Fresenius-Foundation, Bad Homburg v. d. H., Germany.

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Correspondence to Thomas Skurk.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Beate Brandl Née: Ott

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Supplemental Figure 1

Multidimensional scaling (MDS) plot of phylogenetic distances (β-diversity). Non-obese: non-obese group, n = 17; PPI V1: obese patients with PPI medication before surgery, n = 5; no PPI V1: obese patients without PPI medication before surgery, n = 12; PPI V2: obese patients with PPI medication 6 months after surgery, n = 7; no PPI V2: obese patients without PPI medication 6 months after surgery, n = 10. (PNG 356 kb)

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Kellerer, T., Brandl, B., Büttner, J. et al. Impact of Laparoscopic Sleeve Gastrectomy on Gut Permeability in Morbidly Obese Subjects. OBES SURG 29, 2132–2143 (2019). https://doi.org/10.1007/s11695-019-03815-6

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