Lack of support for a common etiology in Johne's disease of animals and Crohn's disease in humans

Abstract

Summary:The superficial similarity of Johne's disease to Crohn's disease led to the hypothesis that, like the former, Crohn's disease was caused by Mycobacterium paratuberculosis. Detailed pathologic comparisons, however, reveal little similarity between these two entities, including the lack of important extraintestinal manifestations. Attempts to recover M. paratuberculosis by culture have only rarely succeeded and the significance of spheroplasts that appear more frequently on culture is seriously in question. Five immunocytochemistry studies have failed to find mycobacterial antigens in diseased tissues and the five most recent polymerase chain reaction (PCR) attempts to find genomic evidence of M. paratuberculosis were uniformly negative. Numerous serologic studies failed to demonstrate antibody to M. paratuberculosis and attempts to show cell-mediated immunity were also unrewarding. Inoculation of numerous experimental animals with Crohn's disease tissue has failed to induce Johne's disease, and inoculation of various animal species with M. paratuberculosis has equally failed to result in Crohn's disease. Controlled studies of the treatment of Crohn's disease with antimycobacterial agents have generally resulted in no improvement, and most studies that have shown a positive response are either uncontrolled or include broad-spectrum antibiotics that may be acting on pathogens other than mycobacteria. Finally, although Johne's disease is common in farm animals, and infected animals shed M. paratuberculosis in large numbers, no record of zoonotic transmission has been recorded. Key Words: Crohn's diseaseMycobacteria-Johne's disease-Zoonoses-Spheroplasts.Among research scientists, public health veterinarians, and the milk-consuming public there continues to be concern about the possibility that Mycobacterium paratuberculosis, the causative agent of Johne's disease (JD) of ruminants, is transmissible to humans and that it causes Crohn's disease (CD). Since the hypothesis that M. paratuberculosis causes CD was first mooted, much evidence that argues against it has accumulated. The purpose of this article is to summarize this evidence and to review the relationship between JD of animals and CD. PATHOLOGYA statement that is reiterated often is that which claims that CD is remarkably similar to JD. This author contends that the morphologic similarities are superficial, and in light of current histopathologic interpretation, more suggestive of differing etiopathogenesis.Address correspondence and reprint requests Lo Dr. H. J. Van Kruiningen, Department of Pathobiology, University of Connecticut, 61 N. Eagleville Rd., U-89, Storrs, CT 06269-3089, U.S.A.Manuscript received November 19, 1998; accepted March 24, 1999. Crohn's disease is a chronic, segmental disease of the intestine; it is submucosal and transmural, fibrosing, sclerosing, and stenosing (1-6). Affected most frequently are the distal ileum and proximal colon; however, CD sometimes occurs in other portions of the gastrointestinal tract. Segmental disea...

Mycobacterium avium in the Postgenomic Era

“…paratuberculosis DNA found in CD patient samples, ulcerative colitis patient samples, and healthy controls, in various proportions (53,187,255). The controversy will likely continue, and it is not our intention to recapitulate the many arguments presented for and against the hypothesis; 20% of publications containing the terms "Crohn" and "paratuberculosis" are review articles, and the following references address some of these issues (13,36,37,40,105,106,111,115,213,230,242,281,286).…”

Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases

“…Considerable controversy remains, however, as to whether the entire commensal microbiota or individual pathogens [e.g., Mycobacterium avium spp. paratuberculosis (MAP)] are primarily responsible for induction of inflammation (19)(20)(21)(22)(23)(24).…”

Mycobacterium Avium Subspecies Paratuberculosis

“…The hypothesis that Mycobacterium paratuberculosis is the cause of Crohn's disease is older than 100 years (Dalziel, 1913). In particular, it necessary to emphasized that a lot of the controversy (Van Kruiningen, 1999) concerning MAP and CD stems from inconsistent methodology used to detect and isolate MAP, which have questioned the causal (Naser et al, 2014) …”