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Assessment of the Intestinal Barrier with Five Different Permeability Tests in Healthy C57BL/6J and BALB/cJ Mice

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Abstract

Background

Intestinal permeability is thought to be of major relevance for digestive and nutrition-related diseases, and therefore has been studied in numerous mouse models of disease. However, it is unclear which tools are the preferable ones, and how normal values should be defined.

Aims

To compare different in vivo permeability tests in healthy mice of commonly used genetic backgrounds.

Methods

We assessed the intestinal barrier in male and female C57BL/6J and BALB/cJ mice of different ages, using four orally administered permeability markers, FITC-dextran 4000 (FITC-D4000) and ovalbumin (OVA) measured in plasma, and polyethylene glycol (PEG) and lactulose/mannitol (Lac/Man) measured in urine, and by assessing lipopolysaccharide (LPS) in portal vein plasma.

Results

After gavage, FITC-D4000, OVA, Lac/Man, and PEG400, but not PEG4000, were detectable in plasma or urine. Female mice tended to have a higher permeability according to the FITC-D4000, OVA, and PEG400 tests, but the Lac/Man ratio was higher in males. No significant differences between the two mouse strains of young and old mice were observed except for mannitol recovery, which was higher in BALB/cJ mice compared to C57BL/6J mice (p < 0.05). Virtually no LPS was detected in healthy mice. For all markers, normal values have been defined based on 5th–95th percentile ranges of our data.

Conclusion

Selected oral permeability tests, such as FITC-D4000, OVA, PEG400, and Lac/Man, as well as LPS measurements in portal vein plasma, could be suitable for the evaluation of the intestinal barrier in mice, if used in a standardized way.

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References

  1. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9:799–809.

    Article  CAS  PubMed  Google Scholar 

  2. Camilleri M, Madsen K, Spiller R, Greenwood-Van Meerveld B, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil. 2012;24:503–512.

    Article  CAS  PubMed  Google Scholar 

  3. Pastorelli L, De Salvo C, Mercado JR, Vecchi M, Pizarro TT. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol. 2013;4:280.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Bischoff SC, Barbara G, Buurman W, et al. Intestinal permeability—a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Grootjans J, Thuijls G, Verdam F, Derikx JP, Lenaerts K, Buurman WA. Non-invasive assessment of barrier integrity and function of the human gut. World J Gastrointest Surg. 2010;2:61–69.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Wang L, Llorente C, Hartmann P, Yang AM, Chen P, Schnabl B. Methods to determine intestinal permeability and bacterial translocation during liver disease. J Immunol Methods. 2015;S0022–1759:00005–00008.

    Google Scholar 

  7. Nejdfors P, Ekelund M, Jeppsson B, Weström BR. Mucosal in vitro permeability in the intestinal tract of the pig, the rat, and man: species- and region-related differences. Scand J Gastroenterol. 2000;35:501–507.

    Article  CAS  PubMed  Google Scholar 

  8. Cani PD, Rodrigo B, 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;57:1470–1481.

    Article  CAS  PubMed  Google Scholar 

  9. Uhnoo IS, Freihorst J, Riepenhoff-Talty M, Fisher JE, Ogra PL. Effect of rotavirus infection and malnutrition on uptake of a dietary antigen in the intestine. Pediatr Res. 1990;27:153–160.

    Article  CAS  PubMed  Google Scholar 

  10. Yang Z, Chen A, Sun H, Ye Y, Fang W. Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice. Vaccine. 2007;25:161–169.

    Article  CAS  PubMed  Google Scholar 

  11. Parlesak A, Schafer C, Schutz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol. 2000;32:742–747.

    Article  CAS  PubMed  Google Scholar 

  12. Kerckhoffs AP, Akkermans LM, de Smet MB, et al. Intestinal permeability in irritable bowelsyndrome patients: effects of NSAIDs. Dig Dis Sci. 2010;55:716–723.

    Article  CAS  PubMed  Google Scholar 

  13. van Wijck K, Bessems BA, van Eijk HM, Buurman WA, Dejong CH, Lenaerts K. Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: Is it time to choose? Clin Exp Gastroenterol. 2012;5:139–150.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Braga Neto MB, Aguiar CV, Maciel JG, et al. Evaluation of HIV protease and nucleoside reverse transcriptase inhibitors on proliferation, necrosis, apoptosis in intestinal epithelial cells and electrolyte and water transport and epithelial barrier function in mice. BMC Gastroenterol. 2010;10:90.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Vilela EG, Torres HO, Ferrari ML, Lima AS, Cunha AS. Gut permeability to lactulose and mannitol differs in treated Crohn’s disease and celiac disease patients and healthy subjects. Braz J Med Biol Res. 2008;41:1105–1109.

    Article  CAS  PubMed  Google Scholar 

  16. Kubica P, Kot-Wasik A, Wasik A, Namieśnik J, Landowski P. Modern approach for determination of lactulose, mannitol and sucrose in human urine using HPLC-MS/MS for the studies of intestinal and upper digestive tract permeability. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;907:34–40.

    Article  CAS  PubMed  Google Scholar 

  17. Ritze Y, Bárdos G, D’Haese JG, et al. Effect of high sugar intake on glucose transporter and weight regulating hormones in mice and humans. PLoS One. 2014;9:e101702.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Chang JX, Chen S, Ma LP, et al. Functional and morphological changes of the gut barrier during the restitution process after hemorrhagic shock. World J Gastroenterol. 2005;11:5485–5491.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Giorgio V, Miele L, Principessa L, et al. Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity. Dig Liver Dis. 2014;46:556–560.

    Article  PubMed  Google Scholar 

  20. Kless C, Müller VM, Schüppel VL, et al. Diet-induced obesity causes metabolic impairment independent of alterations in gut barrier integrity. Mol Nutr Food Res. 2015;59:968–978.

    Article  CAS  PubMed  Google Scholar 

  21. Yokooji T, Nouma H, Matsuo H. Characterization of ovalbumin absorption pathways in the rat intestine, including the effects of aspirin. Biol Pharm Bull. 2014;37:1359–1365.

    Article  CAS  PubMed  Google Scholar 

  22. Meddings JB, Jarand J, Urbanski SJ, Hardin J, Gall DG. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol. 1999;276:G951–G957.

    CAS  PubMed  Google Scholar 

  23. Anderson AD, Jain PK, Fleming S, Poon P, Mitchell CJ, MacFie J. Evaluation of a triple sugar test of colonic permeability in humans. Acta Physiol Scand. 2004;182:171–177.

    Article  CAS  PubMed  Google Scholar 

  24. Meddings JB, Gibbons I. Discrimination of site-specific alterations in gastrointestinal permeability in the rat. Gastroenterology. 1998;114:83–92.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was funded by the Deutsche Forschungsgemeinschaft (DGF) SPP Intestinal Microbiota 1656, Project “Modulation of the intestinal barrier by the intestinal microbiota—Role of dietetic factors and the mucosal immune system” (BI 424/8-1) to S. C. Bischoff.

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Authors and Affiliations

  1. Department of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70593, Stuttgart, Germany

    Valentina Volynets, Astrid Reichold, Gyöngyi Bárdos, Andreas Rings & Stephan C. Bischoff

  2. Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany

    André Bleich

Authors
  1. Valentina Volynets
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  2. Astrid Reichold
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  3. Gyöngyi Bárdos
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  4. Andreas Rings
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  5. André Bleich
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  6. Stephan C. Bischoff
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Corresponding author

Correspondence to Stephan C. Bischoff.

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The authors declare that they have no conflict of interest.

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Volynets, V., Reichold, A., Bárdos, G. et al. Assessment of the Intestinal Barrier with Five Different Permeability Tests in Healthy C57BL/6J and BALB/cJ Mice. Dig Dis Sci 61, 737–746 (2016). https://doi.org/10.1007/s10620-015-3935-y

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  • DOI: https://doi.org/10.1007/s10620-015-3935-y

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