リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「炎症性腸疾患患者の腸内細菌に対する免疫グロブリンを介した応答および菌種の解析」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

炎症性腸疾患患者の腸内細菌に対する免疫グロブリンを介した応答および菌種の解析

枡 悠太郎 東北大学

2021.03.25

概要

【背景】炎症性腸疾患 (Inflammatory Bowel Disease; IBD) の病態の一部には腸内細菌叢が関与し、無菌マウスの腸に IgA 被覆化細菌を移植すると腸炎を発症することから、その免疫応答が病態形成や活動性に関わると推測されている。免疫グロブリン (Immunoglobulin; Ig) には複数のサブタイプがあり、それぞれ異なる免疫応答を起こすことが知られている。しかし、腸管内での各Ig サブタイプで被覆化された細菌とその免疫応答の違いについては明らかになっていない。

【目的】IBD 患者の便中の各 Ig に被覆化された細菌を解析し、潰瘍性大腸炎 (Ulcerative Colitis; UC) やクローン病 (Crohn’s disease;CD)に特異的な菌や疾患の活動性と関連する菌叢を明らかにする。【方法】当院通院または入院中の IBD 42 例 (UC 20 例、CD 22 例) および健常人(Healthy control; HC)12例より糞便を回収し、便中の細菌を抽出した。各 Ig で被覆化された細菌をフローサイトメーター (fluoroescence-activated cell sorting; FACS)でソーティングした。得られた細菌の DNA を抽出し、V3-V4 領域のユニバーサルプライマーを使用して 16S ribosomal RNA (16S rRNA) シークエンス解析を行った。併せて、便中に含まれる各 Ig 濃度の測定を行った。

【結果】IBD では HC に比べ IgA、 IgM で被覆化された菌が増加しており、HC では認めない IgG で被覆化された菌の存在が確認された。UC では IgG1~IgG3 および IgM による被覆化細菌率が、CD では IgG3、IgG4、および IgM による被覆化細菌率が疾患活動性と有意に相関していることを確認した。菌叢全体の解析においては IBD ではHC と比べて多様性の低下が確認された。各 Ig 被覆化細菌の解析では、UC では活動性に伴い増加する特定の菌種は同定できなかったが、CD 活動期では Bacteroides ovatus や Strreptcoccus 属の細菌の増加が確認できた。

【結論】疾患活動性において腸内細菌に対する各 Ig サブタイプによる被覆の違いが明らかになり、IBD の病態形成に各 Ig による細菌被覆が関与していることが示唆された。

この論文で使われている画像

参考文献

1. Torres, J., et al., Crohn's disease. Lancet, 2017. 389(10080): p. 1741-1755.

2. Ungaro, R., et al., Ulcerative colitis. Lancet, 2017. 389(10080): p. 1756-1770.

3. Park, S.J., W.H. Kim, and J.H. Cheon, Clinical characteristics and treatment of inflammatory bowel disease: a comparison of Eastern and Western perspectives. World J Gastroenterol, 2014. 20(33): p. 11525-37.

4. Kawaguchi, T., et al., Food antigen-induced immune responses in Crohn's disease patients and experimental colitis mice. J Gastroenterol, 2015. 50(4): p. 394-405.

5. Higuchi, L.M., et al., A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol, 2012. 107(9): p. 1399-406.

6. Silverstein, M.D., et al., Cigarette smoking in Crohn's disease. Am J Gastroenterol, 1989. 84(1): p. 31-3.

7. Sartor, R.B. and G.D. Wu, Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches. Gastroenterology, 2017. 152(2): p. 327-339.e4.

8. Sun, M., et al., Regulatory immune cells in regulation of intestinal inflammatory response to microbiota. Mucosal Immunol, 2015. 8(5): p. 969-978.

9. Kühn, R., et al., Interleukin-10-deficient mice develop chronic enterocolitis. Cell, 1993. 75(2): p. 263-74.

10. Rath, H.C., Role of commensal bacteria in chronic experimental colitis: lessons from the HLA-B27 transgenic rat. Pathobiology, 2002. 70(3): p. 131-8.

11. Ogura, Y., et al., A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature, 2001. 411(6837): p. 603-6.

12. Frank, D.N., et al., Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A, 2007. 104(34): p. 13780-5.

13. Peterson, D.A., et al., Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe, 2008. 3(6): p. 417-27.

14. Nagalingam, N.A. and S.V. Lynch, Role of the microbiota in inflammatory bowel diseases. Inflamm Bowel Dis, 2012. 18(5): p. 968-84.

15. Sheehan, D., C. Moran, and F. Shanahan, The microbiota in inflammatory bowel disease. J Gastroenterol, 2015. 50(5): p. 495-507.

16. Walker, A.W., et al., High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol, 2011. 11: p. 7.

17. Manichanh, C., et al., Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut, 2006. 55(2): p. 205-11.

18. Dorn, I., et al., Lamina propria plasma cells in inflammatory bowel disease: intracellular detection of immunoglobulins using flow cytometry. Immunobiology, 2002. 206(5): p. 546-57.

19. Lin, R., et al., Clinical significance of soluble immunoglobulins A and G and their coated bacteria in feces of patients with inflammatory bowel disease. J Transl Med, 2018. 16(1): p. 359.

20. Rengarajan, S., et al., Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. Gut Microbes, 2020. 11(3): p. 405-420.

21. van der Waaij, L.A., et al., Immunoglobulin coating of faecal bacteria in inflammatory bowel disease. Eur J Gastroenterol Hepatol, 2004. 16(7): p. 669-74.

22. Harmsen, H.J., et al., Crohn's disease patients have more IgG-binding fecal bacteria than controls. Clin Vaccine Immunol, 2012. 19(4): p. 515-21.

23. Lu, L.L., et al., Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol, 2018. 18(1): p. 46-61.

24. Benckert, J., et al., The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J Clin Invest, 2011. 121(5): p. 1946-55.

25. Rachmilewitz, D., Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. Bmj, 1989. 298(6666): p. 82-6.

26. Best, W.R., et al., Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology, 1976. 70(3): p. 439-44.

27. Bolyen, E., et al., Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol, 2019. 37(8): p. 852-857.

28. Callahan, B.J., et al., DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods, 2016. 13(7): p. 581-3.

29. Singh, S.B., et al., Autophagy Genes of Host Responds to Disruption of Gut Microbial Community by Antibiotics. Dig Dis Sci, 2017. 62(6): p. 1486-1497.

30. Bokulich, N.A., et al., Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2's q2-feature-classifier plugin. Microbiome, 2018. 6(1): p. 90.

31. Shannon, C.E., The mathematical theory of communication. 1963. MD Comput, 1997. 14(4): p. 306-17.

32. Nishida, A., et al., Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol, 2018. 11(1): p. 1-10.

33. Wallace, K.L., et al., Immunopathology of inflammatory bowel disease. World J Gastroenterol, 2014. 20(1): p. 6-21.

34. Cario, E. and D.K. Podolsky, Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun, 2000. 68(12): p. 7010-7.

35. Palm, N.W., et al., Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell, 2014. 158(5): p. 1000-1010.

36. Brandtzaeg, P., E.S. Baekkevold, and H.C. Morton, From B to A the mucosal way. Nat Immunol, 2001. 2(12): p. 1093-4.

37. Kett, K. and P. Brandtzaeg, Local IgA subclass alterations in ulcerative colitis and Crohn's disease of the colon. Gut, 1987. 28(8): p. 1013-21.

38. Woof, J.M. and M.W. Russell, Structure and function relationships in IgA. Mucosal Immunol, 2011. 4(6): p. 590-7.

39. Ehrenstein, M.R. and C.A. Notley, The importance of natural IgM: scavenger, protector and regulator. Nat Rev Immunol, 2010. 10(11): p. 778-86.

40. Fadlallah, J., et al., Microbial ecology perturbation in human IgA deficiency. Sci Transl Med, 2018. 10(439).

41. Catanzaro, J.R., et al., IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Sci Rep, 2019. 9(1): p. 13574.

42. Rosekrans, P.C., et al., Immunoglobulin containing cells in inflammatory bowel disease of the colon: a morphometric and immunohistochemical study. Gut, 1980. 21(11): p. 941-7.

43. Scott, B.B., et al., Rectal mucosal plasma cells in inflammatory bowel disease. Gut, 1983. 24(6): p. 519-24.

44. Uo, M., et al., Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation. Gut, 2013. 62(12): p. 1734-44.

45. Preisker, S., et al., Crohn's Disease Patients in Remission Display an Enhanced Intestinal IgM⁺ B Cell Count in Concert with a Strong Activation of the Intestinal Complement System. Cells, 2019. 8(1).

46. Scott, M.G., et al., Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls. Clin Exp Immunol, 1986. 66(1): p. 209-15.

47. Vidarsson, G., G. Dekkers, and T. Rispens, IgG subclasses and allotypes: from structure to effector functions. Front Immunol, 2014. 5: p. 520.

48. Michielan, A. and R. D'Incà, Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. Mediators Inflamm, 2015. 2015: p. 628157.

49. Andoh, A., et al., Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn's disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol, 2011. 46(4): p. 479-86.

50. Yang, C., et al., Fecal IgA Levels Are Determined by Strain-Level Differences in Bacteroides ovatus and Are Modifiable by Gut Microbiota Manipulation. Cell Host Microbe, 2020. 27(3): p. 467-475.e6.

51. Fyderek, K., et al., Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease. World J Gastroenterol, 2009. 15(42): p. 5287-94.

52. Walujkar, S.A., et al., Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis. World J Microbiol Biotechnol, 2018. 34(6): p. 76.

53. Machiels, K., et al., A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut, 2014. 63(8): p. 1275-83.

54. Tyler, A.D., et al., Characterization of the gut-associated microbiome in inflammatory pouch complications following ileal pouch-anal anastomosis. PLoS One, 2013. 8(9): p. e66934.

55. Pascal, V., et al., A microbial signature for Crohn's disease. Gut, 2017. 66(5): p. 813-822.

56. Kump, P., et al., The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. Aliment Pharmacol Ther, 2018. 47(1): p. 67-77.

57. Rajilić-Stojanović, M., et al., Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis, 2013. 19(3): p. 481-8.

58. Fuentes, S., et al., Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. Isme j, 2017. 11(8): p. 1877-1889.

59. Paramsothy, S., et al., Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis, 2017. 11(10): p. 1180- 1199.

60. Xu, J., et al., 5-Aminosalicylic Acid Alters the Gut Bacterial Microbiota in Patients With Ulcerative Colitis. Front Microbiol, 2018. 9: p. 1274.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る