Crohn's disease and related inflammatory diseases: from many single hypotheses to one "superhypothesis"

Abstract

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.Keywords: aerosolisation; asthma; autoimmune diseases; autoinflammatory diseases; bacteri...

Mycobacterium avium subsp. paratuberculosis and microbiome profile of patients in a referral gastrointestinal diseases centre in the Sudan

“…Therefore, MAP could infect humans but remains in latency in those who do not show overt symptoms of infection [ 40 ]. The fact that bacterial cell components and their derivatives trigger inflammatory pathways or autoimmune conditions explain why MAP may not be detected in all specimens [ 41 ] and contrarily it may be detected in genetically non-susceptible individuals [ 42 – 44 ]. Infected animals usually excrete MAP in their faeces and milk, even before developing disease symptoms or showing clinical signs.…”

Neglected Facts on Mycobacterium Avium Subspecies Paratuberculosis and Type 1 Diabetes

“…For further references see Box 3 M. avium subsp. paratuberculosis in [ 26 ] and a review by Hruska and Pavlik [ 27 ].…”

Instrumental analytical tools for mycobacteria characterisation

“…For example, the aim of the determination of M. avium subsp. paratuberculosis (MAP), which causes paratuberculosis in cattle and affects the development of chronic inflammatory and autoimmune diseases in humans, may be the excretion of MAP in milk and faeces or the severity of meat contamination (Hruska and Pavlik 2014;Hruska and Cepica 2019). Interpretation of the obtained results should take into account the course of the disease and the possibility of an intermittent excretion of mycobacteria.…”