Introduction
The potential aetiological relationship between Mycobacterium avium subsp. paratuberculosis (MAP) and Crohn's disease was first proposed over 100 years ago (Dalziel, 1913). This hypothesis was stimulated by clinical and pathological similarities observed between paratuberculosis and Crohn's disease.
Clinically, both conditions are characterized by intermittent diarrhoea and weight loss; pathologically, the conditions often present with disease within the ileocecal area, and the formation of ulcerations and intramural granulomas (Savarino et al., 2019). Yet, several differences between the two diseases have also been noted (Sartor, 2005).The cause of Crohn's disease remains unknown, but it is generally considered to involve a genetically determined immune dysregula- tion to an intestinal microbiological exposure (Abraham and Cho, 2009; Stappenbeck et al., 2011; Kostic et al., 2014). Of note, while a number of MAP-centred reviews discuss the possibilIty of a MAP-Crohn's link (Gitlin et al., 2012; Liverani et al., 2014; Bach, 2015), with varying degrees of conviction, most Crohn's aetiology reviews do not mention MAP, as this is not presently a leading hypothesis among inflammatory bowel disease (IBD) researchers. The reasons for this general lack of interest in the MAP hypothesis are variable but appear to include intellectual fatigue (the hypothesis has not advanced in a century), uncertainty (inconsistent results from different studies) and the limited effect of anti-mycobacterial drugs (16% absolute efficacy of anti-MAP treatment in a clinical trial published by Selby et al., 2007). Each of these will be addressed below, after a review of the data that have accumulated since the previous edition of this book. Our objective is to provide an up- to-date summary of the latest research, which provides evidence for and against the potential relationship between MAP and Crohn's disease (Tables 3.1 and 3.2). In doing so, we intend to identify what remains unresolved and what further studies could ultimately answer this century-old question, one way or the other.
3.2