Glucocorticoid and dietary effects on mucosal microbiota in canine inflammatory bowel disease

English version

Autoři: Todd Atherly ^aff001; Giacomo Rossi ^aff002; Robin White ^aff001; Yeon-Jung Seo ^aff003; Chong Wang ^aff004; Mark Ackermann ^aff005; Mary Breuer ^aff004; Karin Allenspach ^aff001; Jonathan P. Mochel ^aff003; Albert E. Jergens ^aff001
Působiště autorů: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America ^aff001; School of Biosciences and Veterinary Medicine, University of Camerino, Macerata, Italy ^aff002; Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America ^aff003; Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America ^aff004; Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America ^aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226780

Souhrn

The pathogenesis of canine inflammatory bowel disease (IBD) involves complex interactions between mucosal immunity and the intestinal microbiota. Glucocorticoids are commonly administered to reduce mucosal inflammation and gastrointestinal signs. The study objective was to evaluate the effects of diet and oral prednisone on the spatial distribution of mucosal bacteria in IBD dogs. Eight dogs diagnosed with IBD were treated with immunosuppressive doses of prednisone. The mucosal microbiota from endoscopic biopsies of IBD dogs and healthy controls (HC; n = 15 dogs) was evaluated by fluorescence in situ hybridization (FISH) targeting the 16S rRNA genes of total bacteria and bacterial species relevant in canine/human IBD. Apicaljunction protein (AJP) expression using immunohistochemistry investigated the effect of medical therapy on intestinal barrier integrity. All IBD dogs had a reduction in GI signs following diet and prednisone therapy compared with baseline CIBDAI scores (P < 0.05). The mucosal microbiota of HC and diseased dogs was most abundant in free and adherent mucus. Only Lactobacilli were increased (P < 0.05) in the adherent mucus of IBD dogs compared to HC. The spatial distribution of mucosal bacteria was significantly different (P < 0.05) in IBD dogs following prednisone therapy, with higher numbers of Bifidobacteria and Streptococci detected across all mucosal compartments and increased numbers of Bifidobacterium spp., Faecalibacterium spp., and Streptococcus spp. present within adherent mucus. Differences in intestinal AJPs were detected with expression of occludin increased (P < 0.05) in IBD dogs versus HC. The expressions of occludin and E-cadherin were increased but zonulin decreased (P < 0.05 for each) in IBD dogs following prednisone therapy. In conclusion, the spatial distribution of mucosal bacteria differs between IBD and HC dogs, and in response to diet and glucocorticoid administration. Medical therapy was associated with beneficial changes in microbial community structure and enhanced mucosal epithelial AJP expression.

Klíčová slova:

Bacteria – Dogs – Diet – Gastrointestinal tract – Microbiome – Inflammatory bowel disease – Biopsy – Endoscopy

Zdroje

1. Jergens AE. Inflammatory bowel disease. Current perspectives. The Veterinary clinics of North America Small animal practice. 1999;29(2):501–21, vii. Epub 1999/04/15. 10202800.

2. Jergens AE, Moore FM, Haynes JS, Miles KG. Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987–1990). Journal of the American Veterinary Medical Association. 1992;201(10):1603–8. Epub 1992/11/15. 1289345.

3. Simpson KW, Jergens AE. Pitfalls and progress in the diagnosis and management of canine inflammatory bowel disease. The Veterinary clinics of North America Small animal practice. 2011;41(2):381–98. Epub 2011/04/14. doi: 10.1016/j.cvsm.2011.02.003 21486642.

4. Sartor RB, Wu GD. Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches. Gastroenterology. 2017;152(2):327–39.e4. Epub 2016/10/23. doi: 10.1053/j.gastro.2016.10.012 27769810; PubMed Central PMCID: PMC5511756.

5. Packey CD, Sartor RB. Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases. Journal of internal medicine. 2008;263(6):597–606. Epub 2008/05/16. doi: 10.1111/j.1365-2796.2008.01962.x 18479259.

6. Honneffer JB, Minamoto Y, Suchodolski JS. Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs. World journal of gastroenterology. 2014;20(44):16489–97. Epub 2014/12/04. doi: 10.3748/wjg.v20.i44.16489 25469017; PubMed Central PMCID: PMC4248192.

7. Suchodolski JS, Dowd SE, Wilke V, Steiner JM, Jergens AE. 16S rRNA gene pyrosequencing reveals bacterial dysbiosis in the duodenum of dogs with idiopathic inflammatory bowel disease. PloS one. 2012;7(6):e39333. Epub 2012/06/22. doi: 10.1371/journal.pone.0039333 22720094; PubMed Central PMCID: PMC3376104.

8. Suchodolski JS, Xenoulis PG, Paddock CG, Steiner JM, Jergens AE. Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease. Vet Microbiol. 2010;142(3–4):394–400. Epub 2009/12/05. doi: 10.1016/j.vetmic.2009.11.002 19959301.

9. Cassmann E, White R, Atherly T, Wang C, Sun Y, Khoda S, et al. Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies. PloS one. 2016;11(2):e0147321. Epub 2016/02/04. doi: 10.1371/journal.pone.0147321 26840462; PubMed Central PMCID: PMC4740465.

10. Allenspach K, Wieland B, Grone A, Gaschen F. Chronic enteropathies in dogs: evaluation of risk factors for negative outcome. J Vet Intern Med. 2007;21(4):700–8. Epub 2007/08/22. doi: 10.1892/0891-6640(2007)21[700:ceideo]2.0.co;2 17708389.

11. Jergens AE, Crandell J, Morrison JA, Deitz K, Pressel M, Ackermann M, et al. Comparison of oral prednisone and prednisone combined with metronidazole for induction therapy of canine inflammatory bowel disease: a randomized-controlled trial. J Vet Intern Med. 2010;24(2):269–77. Epub 2010/01/07. doi: 10.1111/j.1939-1676.2009.0447.x 20051005.

12. Makielski K, Cullen J, O'Connor A, Jergens AE. Narrative review of therapies for chronic enteropathies in dogs and cats. J Vet Intern Med. 2019;33(1):11–22. Epub 2018/12/14. doi: 10.1111/jvim.15345 30523666; PubMed Central PMCID: PMC6335544.

13. Barnes PJ. Glucocorticosteroids. Handbook of experimental pharmacology. 2017;237:93–115. Epub 2016/11/01. doi: 10.1007/164_2016_62 27796513.

14. Jergens AE, Schreiner CA, Frank DE, Niyo Y, Ahrens FE, Eckersall PD, et al. A scoring index for disease activity in canine inflammatory bowel disease. J Vet Intern Med. 2003;17(3):291–7. Epub 2003/05/31. doi: 10.1111/j.1939-1676.2003.tb02450.x 12774968.

15. Jergens AE, Evans RB, Ackermann M, Hostetter J, Willard M, Mansell J, et al. Design of a simplified histopathologic model for gastrointestinal inflammation in dogs. Veterinary pathology. 2014;51(5):946–50. Epub 2013/11/28. doi: 10.1177/0300985813511123 24280943.

16. Rossi G, Pengo G, Caldin M, Palumbo Piccionello A, Steiner JM, Cohen ND, et al. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease. PloS one. 2014;9(4):e94699. Epub 2014/04/12. doi: 10.1371/journal.pone.0094699 24722235; PubMed Central PMCID: PMC3983225.

17. Janeczko S, Atwater D, Bogel E, Greiter-Wilke A, Gerold A, Baumgart M, et al. The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease. Vet Microbiol. 2008;128(1–2):178–93. Epub 2007/12/07. doi: 10.1016/j.vetmic.2007.10.014 18054447.

18. Jergens AE, Pressel M, Crandell J, Morrison JA, Sorden SD, Haynes J, et al. Fluorescence in situ hybridization confirms clearance of visible Helicobacter spp. associated with gastritis in dogs and cats. J Vet Intern Med. 2009;23(1):16–23. Epub 2009/01/30. doi: 10.1111/j.1939-1676.2008.0211.x 19175715.

19. White R, Atherly T, Guard B, Rossi G, Wang C, Mosher C, et al. Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease. Gut microbes. 2017;8(5):451–66. Epub 2017/07/06. doi: 10.1080/19490976.2017.1334754 28678609; PubMed Central PMCID: PMC5628651.

20. Forbes JD, Van Domselaar G, Bernstein CN. The Gut Microbiota in Immune-Mediated Inflammatory Diseases. Frontiers in microbiology. 2016;7:1081. Epub 2016/07/28. doi: 10.3389/fmicb.2016.01081 27462309; PubMed Central PMCID: PMC4939298.

21. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–5. Epub 2007/08/19. doi: 10.1073/pnas.0706625104 17699621; PubMed Central PMCID: PMC1959459.

22. Xenoulis PG, Palculict B, Allenspach K, Steiner JM, Van House AM, Suchodolski JS. Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease. FEMS Microbiol Ecol. 2008;66(3):579–89. Epub 2008/07/24. doi: 10.1111/j.1574-6941.2008.00556.x 18647355.

23. Mansfield CS, James FE, Craven M, Davies DR, O'Hara AJ, Nicholls PK, et al. Remission of histiocytic ulcerative colitis in Boxer dogs correlates with eradication of invasive intramucosal Escherichia coli. J Vet Intern Med. 2009;23(5):964–9. Epub 2009/08/15. doi: 10.1111/j.1939-1676.2009.0363.x 19678891.

24. Simpson KW, Dogan B, Rishniw M, Goldstein RE, Klaessig S, McDonough PL, et al. Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Infection and immunity. 2006;74(8):4778–92. Epub 2006/07/25. doi: 10.1128/IAI.00067-06 16861666; PubMed Central PMCID: PMC1539603.

25. Dye TL, Diehl KJ, Wheeler SL, Westfall DS. Randomized, controlled trial of budesonide and prednisone for the treatment of idiopathic inflammatory bowel disease in dogs. J Vet Intern Med. 2013;27(6):1385–91. Epub 2013/10/12. doi: 10.1111/jvim.12195 24112400.

26. Dandrieux JR. Inflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same? The Journal of small animal practice. 2016;57(11):589–99. Epub 2016/10/27. doi: 10.1111/jsap.12588 27747868.

27. Gajendran M, Loganathan P, Catinella AP, Hashash JG. A comprehensive review and update on Crohn's disease. Disease-a-Month. 2018;64(2):20–57. doi: 10.1016/j.disamonth.2017.07.001 28826742

28. Salice M, Rizzello F, Calabrese C, Calandrini L, Gionchetti P. A current overview of corticosteroid use in active ulcerative colitis. Expert review of gastroenterology & hepatology. 2019;13(6):557–61. doi: 10.1080/17474124.2019.1604219 30947569

29. Barnes PJ. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006;148(3):245–54. Epub 04/10. doi: 10.1038/sj.bjp.0706736 16604091.

30. Org E, Mehrabian M, Parks BW, Shipkova P, Liu X, Drake TA, et al. Sex differences and hormonal effects on gut microbiota composition in mice. Gut microbes. 2016;7(4):313–22. doi: 10.1080/19490976.2016.1203502 27355107.

31. Noguera JC, Aira M, Pérez-Losada M, Domínguez J, Velando A. Glucocorticoids modulate gastrointestinal microbiome in a wild bird. R Soc Open Sci. 2018;5(4):171743–. doi: 10.1098/rsos.171743 29765642.

32. Igarashi H, Maeda S, Ohno K, Horigome A, Odamaki T, Tsujimoto H. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs. PloS one. 2014;9(9):e107909–e. doi: 10.1371/journal.pone.0107909 25229475.

33. Huang EY, Inoue T, Leone VA, Dalal S, Touw K, Wang Y, et al. Using corticosteroids to reshape the gut microbiome: implications for inflammatory bowel diseases. Inflammatory bowel diseases. 2015;21(5):963–72. doi: 10.1097/MIB.0000000000000332 25738379.

34. Pigneur B, Lepage P, Mondot S, Schmitz J, Goulet O, Dore J, et al. Mucosal healing and bacterial composition in response to enteral nutrition versus steroid based induction therapy—a randomized prospective clinical trial in children with Crohn's disease. Journal of Crohn's & colitis. 2018. Epub 2018/12/13. doi: 10.1093/ecco-jcc/jjy207 30541015.

35. Kalenyak K, Isaiah A, Heilmann RM, Suchodolski JS, Burgener IA. Comparison of the intestinal mucosal microbiota in dogs diagnosed with idiopathic inflammatory bowel disease and dogs with food-responsive diarrhea before and after treatment. FEMS Microbiol Ecol. 2018;94(2). Epub 2017/12/12. doi: 10.1093/femsec/fix173 29228248.

36. Kuhbacher T, Folsch UR. Practical guidelines for the treatment of inflammatory bowel disease. World journal of gastroenterology. 2007;13(8):1149–55. Epub 2007/04/25. doi: 10.3748/wjg.v13.i8.1149 17451192; PubMed Central PMCID: PMC4146986.

37. Bejaoui M, Sokol H, Marteau P. Targeting the Microbiome in Inflammatory Bowel Disease: Critical Evaluation of Current Concepts and Moving to New Horizons. Digestive diseases (Basel, Switzerland). 2015;33 Suppl 1:105–12. Epub 2015/09/15. doi: 10.1159/000437104 26366577.

38. Niessen CM. Tight junctions/adherens junctions: basic structure and function. The Journal of investigative dermatology. 2007;127(11):2525–32. Epub 2007/10/16. doi: 10.1038/sj.jid.5700865 17934504.

39. Martini E, Krug SM, Siegmund B, Neurath MF, Becker C. Mend Your Fences: The Epithelial Barrier and its Relationship With Mucosal Immunity in Inflammatory Bowel Disease. Cell Mol Gastroenterol Hepatol. 2017;4(1):33–46. doi: 10.1016/j.jcmgh.2017.03.007 28560287.

40. Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2007;56(1):61–72. Epub 07/05. doi: 10.1136/gut.2006.094375 16822808.

41. Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, et al. Interleukin-13 Is the Key Effector Th2 Cytokine in Ulcerative Colitis That Affects Epithelial Tight Junctions, Apoptosis, and Cell Restitution. Gastroenterology. 2005;129(2):550–64. doi: 10.1016/j.gastro.2005.05.002 16083712

42. Oshima T, Miwa H, Joh T. Changes in the expression of claudins in active ulcerative colitis. Journal of Gastroenterology and Hepatology. 2008;23(s2):S146–S50. doi: 10.1111/j.1440-1746.2008.05405.x 19120888

43. Ridyard AE, Brown JK, Rhind SM, Else RW, Simpson JW, Miller HR. Apical junction complex protein expression in the canine colon: differential expression of claudin-2 in the colonic mucosa in dogs with idiopathic colitis. The journal of histochemistry and cytochemistry: official journal of the Histochemistry Society. 2007;55(10):1049–58. Epub 2007/06/28. doi: 10.1369/jhc.7A7211.2007 17595339.

44. Jergens AE, Guard BC, Redfern A, Rossi G, Mochel JP, Pilla R, et al. Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs. Frontiers in Veterinary Science. 2019;6(199). doi: 10.3389/fvets.2019.00199 31316997

Glucocorticoid and dietary effects on mucosal microbiota in canine inflammatory bowel disease

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