Crohn’s disease and related inflammatory diseases: from many single hypotheses to one “superhypothesis”

Abstract

The aetiology of Crohn’s disease and paratuberculosis are the subjects of intensive study and also frequently, of dispute. However, a number of other nosological entities have a similar history, namely type 1 diabetes, multiple sclerosis, sarcoidosis, asthma, psoriasis, spondylarthritis, Blau syndrom etc. The zoonotic risk of Mycobacterium avium subsp. paratuberculosis (MAP) has been discussed for more than one hundred years. „The problem remains open, further research is needed“, is the sentence which seems to be obligatory in the conclusions of many scientific articles. A number of hypotheses have been suggested, all with a grain of truth in them. The infection hypothesis has many supporters and opponents, but it does not fit to all Crohn’s disease cases. The contribution of the genetic factor has been admitted a long time ago and has been experimentally confirmed by recent excellent studies. An environmental factor is expected and has been often mentioned, but has yet to be discovered. Muramyl dipeptide, derived from peptidoglycans of the bacterial cell wall is one of the triggers, mentioned in connection with chronic inflammatory diseases. The immunomodulatory ability of this compound has been recognised for decades and is exploited in Freund’s adjuvant. A critical amount of muramyl dipeptide can affect immunity during some bacterial infections but the long latent period between infection and onset of the clinical form of the disease could explain why a causative relationship between the primary infection and chronic inflammation is not considered. Different species of mycobacteria can be found in the environment, in water, dust, soil and aerosol. Although severe infections with mycobacteria have been described, these species are not thought to be typical zoonotic pathogens. Muramyl dipeptide derived from mycobacteria obviously plays a starring role as a bacterial trigger in the aetiology of many autoimmune and autoinflammatory diseases. Paratuberculosis in cattle and other ruminants is a source of enormous contamination of the environment but also of milk and meat by MAP. Muramyl dipeptide from mycobacteria, namely MAP, and Crohn’s disease as a representative of diseases often called civilization threats, are important pieces of the gigantic puzzle. Mycobacteria in the environment and foodstuffs have to be acknowledged as a public health risk, which can never be completely eliminated. There is no reason to push the panic button, but we must learn how to live together with this microorganism, how the pool of immunomodulator sources can be diminished, and how the pathogenic relationship between triggers and target tissues can be disrupted. The dissemination of knowledge, the availability of rapid and inexpensive tools for identification of mycobacteria in different matrices, and the establishment of a maximal allowed limit for mycobacteria in milk and meat should contribute to food safety and consumer protection.