In the search of a cause of Crohn’s disease

Abstract

While the exact cause of Crohn's disease (CD) is not known, it is thought that chronic inflammation in CD results from an inappropriate and chronic activation of the innate and adaptive mucosal immune systems in a genetically susceptible host, and that enteric microflorae play a pivotal role in the initiation and maintenance of the disease. 1 Organisms such as Pseudomonas maltophilia, Mycobacterium kansasii, Chlamydia trachomatis, Bacteroides fragilis, Listeria monocytogenes, Escherichia coli and Mycobacterium avium subspecies paratuberculosis (MAP) have been implicated and identified in the intestines of patients with CD; however, no other putative pathogenic organism except MAP causes a chronic granulomatous inflammation of the intestines in every other species in which it is present. 2 Moreover, because of remarkable clinical, morphological and epidemiological similarity between intestinal tuberculosis (caused by Mycobacterium tuberculosis) and CD in humans and Johne's disease (caused by Mycobacterium avium paratuberculosis) in cattle, a mycobacterial pathogen is thought to be a causative organism of CD. [3][4][5][6][7] An association and causality of Helicobacter pylori with peptic ulcer disease revolutionized the treatment of peptic ulcers; similar implication of MAP as a cause of CD has raised hopes amongst physicians, microbiologists and basic scientists for the cure of this disease. 8 In the first report almost 25 years back, Chiodini and colleagues isolated cell-wall deficient cells, called spheroplasts, from tissue samples after several months of incubation from patients with CD. These spheroplasts were sub-cultured and they later developed a cell wall that stained positively with Ziehl-Neelson staining; they were classified as mycobacterial like organisms. 9-11 These isolates were later confirmed as M. avium paratuberculosis by DNA hybridization. The unusual nature of the cell walldeficient MAP and the challenges in culture of MAP with its fastidious and slow growing requiring months to years to culture and multiple studies reporting failure to culture MAP from patients with CD dampened the initial zeal. 12 There was then a period of silence in the 1990s. With availability of better culture techniques and use of molecular techniques to identify MAP in 2000s, there was resurgence of interest of many laboratories in this field. There has been a flurry of publications since then relating CD and MAP. [13][14][15][16][17][18][19][20][21][22][23][24][25] MAP infection in humans is difficult to detect. The organisms are intracellular and minimize their own immune recognition. They are therefore difficult to isolate and propagate in culture and are relatively resistant to chemical and enzymatic lysis. Reliable access to their DNA is only achieved during sample processing by combining exposure to stringent lysis buffers with an additional optimised mechanical disruption step. Freezing samples and tissue extracts especially at -20°C substantially reduces the PCR detection rate of their GC-rich DNA. The identifi...

Mycobacterium aviumsubspeciesparatuberculosis –an important food borne pathogen of high public health significance with special reference to India: an update

“…Meat can also be contaminated with fecal material loaded with MAP bacilli during slaughter and procedures used for evisceration and processing of meat. MAP might be present in pasteurized milk (Slana et al 2008), infant formulation made from pasteurized milk (Lund et al 2002;Makharia and Singh 2009), breast milk of a woman suffering from Crohn's disease (CD) (Naser et al 2009). The National Association for Colitis and Crohn's disease (NACC) in UK commissioned a report from an expert review group into the evidence linking MAP and Crohn's disease in 2003 (NACC 2003).…”

Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp

“…Manipulating gut flora using probiotics may correct and/or prevent dysregulated immune function in UC; the effects of probiotic bacteria on DC, which are so pivotal in early bacterial recognition and shaping T‐cell responses are likely to be central in immunomodulation by these bacteria. The probiotic mixture VSL#3 was effective in the treatment of patients with mild to moderately active UC, with a response rate of 50–70% and in animal models VSL#3 altered the phenotype and the distribution of DC in the gut mucosa in vivo . Furthermore, oral administration of VSL#3 in UC patients had direct regulatory effects on human gut DC in vivo that were likely to contribute to therapeutic benefit .…”