Skip to main content
SpringerLink
Log in

Experimental disease in infant goats induced by aMycobacterium isolated from a patient with Crohn's disease

A preliminary report

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Pilot studies were done to assess the pathogenicity of aMycobacterium which had been recovered from the diseased ileum of a patient with Crohn's disease. In four separate studies, pairs of infant goats served as subjects. One of each pair received an oral inoculum of freshly harvestedMycobacterium species strain Linda suspended in cream. A littermate or stablemate which received only cream served as control. Necropsies were done at three, five, six, and 10 months postinoculation. Each of the four inoculated animals developed segmental granulomatous disease of the ileum or ileum and more proximal segments of small intestine, and regional lymph nodes. The earliest lesion occurred in Peyer's patches of the ileum and consisted of granulomatous clusters of epithelioid cells and giant cells, without caseation, which often occurred in a mantle of lymphocytes between the germinal centers and the muscularis mucosae. Nine of 10 such granulomas were free of acid-fast bacilli. In more advanced lesions, there was confluence of granulomas and ulceration of the mucosal surface. Two of the four inoculated animals also had lymphocytic lymphangitis in affected segments. Although theMycobacterium Linda was recovered from intestinal segments of all four animals, acid-fast bacteria were not demonstrable in the intestines in two of them. Control animals remained free of lesions and acid-fast bacilli and were negative by bacteriologic culture. TheMycobacterium species strain Linda represents an enteric pathogen capable of inducing granulomas of the distal small intestine of susceptible species. The lesions produced have distinct similarities to those occurring in Crohn's disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chiodini RJ, Van Kruiningen HJ, Thayer WR, Merkal RS, Coutu JA: Possible role of mycobacteria in inflammatory bowel disease. I. An unclassifiedMycobacterium species isolated from patients with Crohn's disease. Dig Dis Sci 29:1073–1079, 1984

    Google Scholar 

  2. Thayer WR, Jr, Coutu JA, Chiodini RJ, Van Kruiningen HJ, Merkal, RS: Possible role of mycobacteria in inflammatory bowel disease. II. Mycobacterial antibodies in Crohn's disease. Dig Dis Sci 29:1080–1085, 1984

    Google Scholar 

  3. Chiodini RJ, Van Kruiningen HJ, Merkal RS, Thayer WR, Jr, Coutu JA: Characteristics of an unclassifiedMycobacterium species isolated from patients with Crohn's disease. J Clin Microbiol 20:966–971, 1984

    Google Scholar 

  4. Chiodini RJ, Van Kruiningen HJ, Thayer WR, Coutu JA, Merkal RS:In vitro antimicrobial susceptibility of aMycobacterium sp. isolated from patients with Crohn's disease. Antimicrob Agents Chemother 26:930–932, 1984

    Google Scholar 

  5. Chiodini RJ, Van Kruiningen HJ, Thayer WR, Coutu JA, Merkal RS: Mycobacterial spheroplasts isolated from patients with Crohn's disease. Gastroenterology 88:1348, 1985

    Google Scholar 

  6. Matthews PRJ, McDiarmid A: The production in bovine calves of a disease resembling paratuberculosis with aMycobacterium sp. isolated from a wood pigeon (Columba palumbus L.). Vet Rec 104:286, 1979

    Google Scholar 

  7. Chiodini RJ, Van Kruiningen HJ, Merkal RS: Ruminant paratuberculosis (Johne's Disease): The current status and future prospects. Cornell Vet 74:218–262, 1984

    Google Scholar 

  8. Crohn BB, Ginzburg L, Oppenheimer G: Regional ileitis — a pathologic and clinical entity. JAMA 99:1323–1329, 1932

    Google Scholar 

  9. Moschcowitz E, Wilensky A: Nonspecific granulomata of the intestine. Am J Med Sci 166:48–66, 1923

    Google Scholar 

  10. Wilensky A, Moschcowitz E: Nonspecific granuloma of the small intestine. Am J Med Sci 173:374–380, 1927

    Google Scholar 

  11. Lockhart-Mummery HE, Morson BC: Crohn's disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut 1:87–105, 1960

    Google Scholar 

  12. McCallum DI, Gray WM: Metastatic Crohn's disease. Br J Dermatol 95:551–554, 1976

    Google Scholar 

  13. Nugent FW, Glaser D, Fernandez-Herlihy I: Crohn's colitis associated with granulomatous bone disease. N Engl J Med 294:262–265, 1976

    Google Scholar 

  14. Menard DB, Haddad H, Blain JG, Beaudry R, Devroede G, Masse S: Granulomatous myositis and myopathy associated with Crohn's colitis. N Engl J Med 295:818–819, 1976

    Google Scholar 

  15. Frayha R, Stevens MB, Bayless TM: Destructive monarthritis and granulomatous synovitis as the presenting manifestions of Crohn's disease. Johns Hopkins Med J 137:151–155, 1975

    Google Scholar 

  16. Beitman RG, Frost SS, Roth JLA: Oral manifestations of gastrointestinal disease. Dig Dis Sci 26:741–747, 1981

    Google Scholar 

  17. Kelly JH, Montgomery WW, Goodman ML, Mulvaney TJ: Upper airway obstruction associated with regional enteritis. Ann Otol Rhinol Laryngol 88:95–99, 1979

    Google Scholar 

  18. Wilder WM, Slagle GW, Hand AM, Watkins WJ: Crohn's disease of the epiglottis, aryepiglottic folds, anus, and rectum. J Clin Gastroenterol 2:87–91, 1980

    Google Scholar 

  19. Mottet NK: Histopathologic spectrum of regional enteritis and ulcerative colitis.In Major Problems in Pathology, Vol II. JL Bennington (ed). Philadelphia, WB Saunders, 1971

    Google Scholar 

  20. Van Patter WN: Pathology and pathogenesis of regional enteritis. PhD dissertation. University of Minnesota, Minneapolis, 1952

    Google Scholar 

  21. Mitchell DN, Rees RJW: Agent transmissible from Crohn's disease tissue. Lancet 2:168–171, 1970

    Google Scholar 

  22. Mitchell DN, Rees RJW: Further observations on the transmissibility of Crohn's disease. Ann NY Acad Sci 278:546–559, 1976

    Google Scholar 

  23. Cave DR, Mitchell DN, Brooke BN: Experimental animal studies of the etiology and pathogenesis of Crohn's disease. Gastroenterology 69:618–624, 1975

    Google Scholar 

  24. Cave DR, Mitchell DN, Brooke BN: Evidence for an agent transmissible from ulcerative colitis tissue. Lancet 1:1311–1315, 1976

    Google Scholar 

  25. Cave DR, Mitchell DN, Brooke BN: Induction of granulomas in mice by Crohn's disease tissue. Gastroenterology 75:632–637, 1978

    Google Scholar 

  26. Cave DR, Mitchell DN, Kane SP, Brooke BN: Further animal evidence of a transmissible agent in Crohn's disease. Lancet 2:1120–1122, 1973

    Google Scholar 

  27. Simonowitz D, Block GE, Riddell RH, Kraft SC, Kirsner JB: The production of an unusual tissue reaction in rabbit bowel injected with Crohn's disease homogenates. Surgery 82:211–218, 1977

    Google Scholar 

  28. Ahlberg J, Bergstrand O, Gillstrom P, Holstrom B, Kronevi T, Reiland S: Negative findings in search for a transmissible agent in Crohn's disease. Acta Chir Scand (Suppl) 482:45–47, 1978

    Google Scholar 

  29. Bolton PM, Owen E, Heatley RV, Jones Williams W, Hughes LE: Negative findings in laboratory animals for a transmissible agent in Crohn's disease. Lancet 2:1122–1124, 1973

    Google Scholar 

  30. Heatley RV, Bolton PM, Owen E, Jones Williams W, Hughes LE: A search for a transmissible agent in Crohn's disease. Gut 16:528–532, 1975

    Google Scholar 

  31. Donnelly BJ, Delaney PV, Healy TM: Evidence for a transmissible factor in Crohn's disease. Gut 18:360–363, 1977

    Google Scholar 

  32. Sachar DB, Taub RN, Janowitz HD: A transmissible agent in Crohn's disease? New pursuit of an old concept. N Engl J Med 293:354–355, 1975

    Google Scholar 

  33. Taub RN, Sachar D, Janowitz HD, Siltzbach LE: Induction of granulomas in mice by inoculation of tissue homogenates from patients with inflammatory bowel disease and sarcoidosis. Ann NY Acad Sci 278:560–564, 1976

    Google Scholar 

  34. Yardley J: Quoted by Thayer W, in Executive Summary of the A.G.A.-N.F.I.C. Sponsored Workshop on Infectious Agents in Inflammatory Bowel Disease. Dig Dis Sci 24:781–784, 1979

    Google Scholar 

  35. Das KM, Morecki R, Lev M: Crohn's disease lymph node homogenates produce murine lymphoma in athymic mice. Gastroenterology 76:1117, 1979

    Google Scholar 

  36. Das KM, Valenzuela I, Williams SE, Soeiro R, Kadish AS, Baum SG: Studies of the etiology of Crohn's disease using athymic nude mice. Gastroenterology 84:364–374, 1983

    Google Scholar 

  37. Hadfield G: The primary histological lesion of regional ileitis. Lancet 2:773–775, 1939

    Google Scholar 

  38. Rickert RL, Carter HW: The “early” ulcerative lesion of Crohn's disease: Correlative light and scanning electron microscopy studies. J Clin Gastroenterol 2:11–19, 1980

    Google Scholar 

  39. Buergelt CD, Hall C, McEntee K, Duncan JR: Pathological evaluation of paratuberculosis in naturally infected cattle. Vet Pathol 15:196–207, 1978

    Google Scholar 

  40. Ellsworth S, Kirkbride CA, Johnson DD: Excretion ofMycobacterium avium from lesions in the intestine and tonsil of swine. Am J Vet Res 41:1526–1530, 1980

    Google Scholar 

  41. Holmberg CA, Henrickson RV, Malaga C, Schneider R, Gribble D: Nontuberculous mycobacterial disease in rhesus monkeys. Vet Pathol 19(Suppl 7):9–16, 1982

    Google Scholar 

  42. Jubb KBK, Kennedy PC: Pathology of Domestic Animals, Vol 2. New York, Academic Press, 1963, pp 122–127

    Google Scholar 

  43. Nakamatsu M, Tujimoto Y, Satoh H: The pathological study of paratuberculosis in goats, centered around the formation of remote lesions. Jpn J Vet Sci 16:103–119, 1968

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathobiology, University of Connecticut, 06268, Storrs, Connecticut

    H. J. Van Kruiningen DVM, PhD, Rodrick J. Chiodini PhD, Walter R. Thayer MD, Jessica A. Coutu BA, Richard S. Merkal PhD & Paul L. Runnels DVM

  2. Division of Gastroenterology, Rhode Island Hospital and Brown University, 02902, Providence, Rhode Island

    H. J. Van Kruiningen DVM, PhD, Rodrick J. Chiodini PhD, Walter R. Thayer MD, Jessica A. Coutu BA, Richard S. Merkal PhD & Paul L. Runnels DVM

  3. The National Animal Disease Laboratory, 50010, Ames, Iowa

    H. J. Van Kruiningen DVM, PhD, Rodrick J. Chiodini PhD, Walter R. Thayer MD, Jessica A. Coutu BA, Richard S. Merkal PhD & Paul L. Runnels DVM

Authors
  1. H. J. Van Kruiningen DVM, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rodrick J. Chiodini PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Walter R. Thayer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jessica A. Coutu BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard S. Merkal PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul L. Runnels DVM
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

The research was supported by grants from the National Foundation for Ileitis and Colitis and the National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases (1-R01-A 31799-01A2) and is submitted as Scientific Contribution No. 1128, Storrs Agricultural Experiment Station, University of Connecticut, Storrs, Connecticut 06268.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Kruiningen, H.J., Chiodini, R.J., Thayer, W.R. et al. Experimental disease in infant goats induced by aMycobacterium isolated from a patient with Crohn's disease. Digest Dis Sci 31, 1351–1360 (1986). https://doi.org/10.1007/BF01299814

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01299814

Keywords

Search

Navigation