Objective: This systematic review assesses the causal relationship between Mycobac-terium avium subspecies paratuberculosis (MAP) and Crohn’s disease (CD).
Methods: A systematic review and meat-analysis of some impressive PCR based stud-ies is provided aimed to answer among other questions the following question. Is there a cause effect relationship between Mycobacterium avium subspecies paratuberculosis and Crohn’s disease? The method of the conditio per quam relationship was used to proof the hypothesis whether the presence of Mycobacterium avium subspecies paratuberculosis guarantees the presence of Crohn’s disease. In other words, if Crohn’s disease is present, then Mycobacterium avium subspecies paratuberculosis is present too. The mathematical formula of the causal relationship k was used to proof the hypothesis, whether there is a cause effect relationship between Mycobacterium avium subspecies paratuberculosis and Crohn’s disease. Significance was indicated by a p-value of less than 0.05.
Results: The studies analyzed (number of cases and controls N=1076) were able to pro-vide evidence that Mycobacterium avium subspecies paratuberculosis is a necessary condition (a conditio sine qua non) and sufficicent conditions of Crohn’s disease. Fur-thermore, the studies analyzed provide impressive evidence of a cause-effect relation-ship between Mycobacterium avium subspecies paratuberculosis and Crohn’s disease.
Conclusion: Mycobacterium avium subspecies paratuberculosis is the cause of Crohn’s disease (k=+0,377468824, p value < 0.0001).
Keywords: Mycobacterium avium subspecies paratuberculosis, Crohn’s disease, cause effect relationship, causality
1. Introduction
Crohn’s disease, described in 1904 by Polish surgeon Antoni Le”niowski [1], later in 1913 by Dalziel [2] and ultimately by Crohn, Ginzburg and Oppenheimer in 1932 [3], is a debilitating chronic inflammatory bowel disease (IBD) of unknown cause. Le”niowski -Crohn’s disease affects about 6.3 per 100,000 people-years in Europe [4]. Many times, the initial signs and symptoms of Crohn’s disease (CD) are non-specific and can overlap with symptoms of irritable bowel syndrome (IBS). A delay in the diagnosis of this inflammatory bowel disease (IBD) is associated with problems for both patients and physicians. Often Crohn’s disease patients suffer from abdominal pain, malabsorption, steatorrhea, protein losing enteropathy, excessive diarrhea, rapid weight loss and other symptoms which may affect their quality of life [5]. Several different extra-intestinal complications of Crohn’s disease (events outside the gastrointestinal tract) may occur. Lesions of Crohn’s disease begin as mucosal erosions and neutrophil infiltrates within crypts and crypt abscesses and may progress to transmural lymphogranulomatous enteritis while a cobblestoned appearance in the distal ileum and colon is observed in Crohn’s disease patients [6]. Medical treatment of Crohn’s disease patients includes nutritional therapy, a medication having weak anti-MAP activity with anti-inflammatory drugs, immunosuppressants, and sometimes antibiotics too. A view monoclonal antibodies such as Adalimumab (Humira ”) and Infliximab (Remicade ”) are used too, to treat Crohn’s disease patients. Most often, Crohn’s disease patients require a dangerous, costly and time-consuming surgical intervention (laparoscopy, strictureplasty, anastomosis, bypass surgery et cetera). A number of theories regarding the etiology of Crohn’s disease are discussed including diet, infections, other unidentified environmental factors, immune dysregulation and autoimmune theories. Still, the cause of Crohn’s disease or some critical aspects in the pathogenesis of this disease are not known. Many authors are of the opinion that Crohn’s disease is a syndrome caused by several etiologies. Mycobacterium avium subspecies paratuberculosis (MAP) is endemic in the bovine populations of many countries [7] and known to be a causative agent of Johne’s disease, an inflammatory bowel disease in a variety of mammals including monkeys, chimpanzees cattle sheep, deer, bison et cetera. Johne’s disease was discovered by Dr. H.A. Johne and Dr. L. Frothingham as visiting scientists from the Pathology Unit in Boston, Massachusetts at the Veterinary Pathology Unit in Dresden by investigating the tissues of a cow from the Oldenburg region of Germany. The first occurrence of Johne’s disease [8] in the U.S. was published by Leonard Pearson (1868-1909) in 1908. The first description of the similarities between Crohn’s disease and Johne’s disease in cattle was made in 1913 by the Scottish surgeon Thomas Kennedy Dalziel [2]. The zoonotic capacities of MAP [9] and transmission routes to humans [10], [11] have been discussed widely. Mycobacterium avium subsp. paratuberculosis has been detected in retail cheese in about 31.7% of the samples [12]. Due to the similarities between Johne’s disease in cattle and Crohn’s disease, it has been argued that Mycobacterium avium subspecies paratuberculosis (MAP), which causes Johne’s disease, might also be a cause of Crohn’s disease too. Historically, MAP became the leading infectious candidate as the causative agent of Crohn’s disease. Meanwhile, the evidence to support a M. paratuberculosis infection as a cause of Crohn’s disease is mounting rapidly. Studies were able to document that up to 83% of Crohn’s patients showed evidence of serum antibodies [13]-[18] to M. avium ss paratuberculosis. In particular, critics of the mycobacterial theory argue that MAP is not a causal factor but a secondary invader [19]. The relationship between Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) and Crohn’s disease is suspected but the evidence remains controversial.