There are two forms of inflammatory bowel diseases (IBD):
   - Ulcerative colitis (UC)
   - Crohn´s disease (CD).

Ulcerative colitis is characterized by recurring episodes of inflammation of the mucosal layer of the large bowel not related to an intestinal infection.

Crohn's disease is characterized by recurring episodes of suppurative inflammation of any part of the bowel, from the mouth to the anus. In addition, clinicians should be aware that some ocular diseases, such as uveitis and scleritis, might precede a diagnosis of UC or CD (Yilmaz et al., 2007). There has been a noticeable increase in the incidence of CD in the northern nations of Western Europe and in North America throughout the 1950s and 1960s. By the early 1980s, this general increase appeared to have come to an end. Small surveys in some European countries report incidence rates of CD ranging from 50 to 80 /million/year. The incidence of infant CD is, however, slightly increasing, resulting from improving earlier diagnosis rather than a more general increase in incidence in young people.

Latest data indicating an IBD incidence of about 200 out of 106 people/year, thus, in many parts of Europe 1 % of the population will sicken with IBD at least once in their lifetime (Richard F Logan 1998).

The pathogenesis of IBD is complex and not completely elucidated. It involves at least three interacting elements:

• genetic susceptibility factors,

• enteric microflora
• immune-mediated tissue injury.

In CD, downstream effector pathways that elicit tissue injury are similar to those in immune mediated diseases affecting other organs: Influx of inflammatory cells from the blood and increased concentration of cytokines, free radicals and lipid mediators. CD represents a complex genetic disease but also tends to occur in families. A spouse risk has been identified for CD indicating a strong correlation between environmental factors and pathogenesis.
Genes associated with this disease are located on chromosomes # 1, 5, 6, 12, 14, 16 and 19. Different polymorphisms of the Nod2 gene may also be responsible for the disease phenotype. Nod2 is expressed in the cytosole of epithelial cells, macrophages and DC. It regulates the signaltransduction pathway by activating NFkappaB.
Nod2-mutations can lead to a decreased immune defence against gut bacteria due to reduced production of defences by gut epithelium cells. Two more genes have been identified: OCTN (organic kation transporter) and DGL5 (Guanylat kinase), both suspected important in epithelial permeability, and disruption of this function leads to defective mucosal immune reaction to bacterial infections.

These factors govern the lifelong crosstalk between host and intestinal flora. A popular theory regarding the pathogenesis of IBD emanates from the initiation and perpetuation of the intestine inflammation as results of an abnormal host response to the endogenous microflora.

Altered microbiota in patients with IBD?
Patients with CD show a microflora reduced in diversity by up to 50 % as compared to healthy persons and by 30 % as compared to ulverative colits. The reduction in diversity in IBD patients arise from loss of non-pathogenic anaerobic bacteria such as Bacteroides-, Eubacterium- and Lactobacillus-species. Thus, no wonder why therapy with live bacteria (probiotics) was argued a promising approach to prevent IBD-relapse. Randomized clinical trials are still required to further define the role of probiotics as preventive and therapeutic agents. In the latest intervention studies using live, non-pathogenic bacteria as treatment for CD the promising results from animal models and some intervention trials could not be repeated. Some authors suggest the choice of strains and knowledge about sufficient doses to be better elucidated

The treatment of IBD focuses on the amelioration of symptoms and prevention of relapse of inflammatory episodes.
The role of endogenous microflora in IBD is confirmed by the long clinical observations that the two most important medications used for treatment of IBD - sulfasalazine and its derivative 5-aminosalicylate (mesalazine, 5-ASA) - have antibacterial activity. Thus, it was postulated that the flare of UC and CD might correlate with the presence of intestinal bacteria. Sulfasalazine has been used for more than 50 years and is highly effective in UC-therapy. An suitable treatment for active CD should rapidly and reliably induce remission, and chronic maintaining therapy aims at prevention of relapses.

The current treatment for active CD as well as UC is based on the use of five classes of drugs:

• non-specific anti-inflammatory drugs such as the 5-ASA, glucocorticoids,
• antimetabolites (e.g. azathioprine of 6-mercaptopurine),
• monoclonal antibodies (e.g. infliximab)
• and antibiotics
  

The chronic inflammation in the gastrointestinal wall of IBD-patients presumably results from abnormal host response to the endogenous microflora. Thus, modification of host bacteria with antibiotics or probiotics could have beneficial effect on the progression of IBD. Miroorganisms tested for IBD-cure are: E.coli (Nissle, 1917), Saccharomyces boulardii, Lactobacillus GG, Lactobacillus shirota etc. Moderate improvements of well-being could be observed in patients with UC.
In CD-patients, maintenance therapy with 5-ASA plus a probiotic preparation appeared significantly more effective in preventing a relapse than solely 5-ASA. Many studies confirm that probiotic treatment alone could not prevent a CD-relapse, other than a combination with anti-inflammatory medication.

Latest approaches combining anti-inflammatory medication with live probiotic bacteria showed promising results. The dietary treatment of IBD aims at improvement of nutrition status, because loss of bone mass and iron deficiency anemia are common complications in patients suffering from IBDs. Yet, no dietary regimen is known preventing inflammatory bowel diseases.

Dietary approaches
Yet, no IBD-prevention is known. Special diets as IBD-cure aim at ameliorating the nutrient supply of patients. Metabolic bone disease and fractures are common in IBD. Patients with UC tend to have a higher prevalence of low bone mass and, thus, higher bone fracture risk than patients with CD.
In contrast, hyperparathyroidism associated with vitamin D deficiency was more prevalent in CD-patients. This finding suggests a different etiologic mechanism of low bone mass in patients with CD. The reported prevalence of anemia varied between 6.2% and 73.7%, with higher reported frequencies in older studies and in in-patients. Iron deficiency is the most likely reason for anemia. Vitamin B12 deficit is associated with the extent of ileal resection but has rarely impact on anemia. Oral iron supplementation may compensate the Fe-lack for short periods but possible intolerance leads to discontinuation in up to 21%. Eleven out of eleven studies show that oral iron revenue enhances intestinal inflammation and colon carcinogenesis in animal models of colitis. Intravenous iron supplementation with iron sucrose has been tested in over 250 CD-patients, is assumed safe, effective and does not entail such risks. However, further studies regarding the safety and effectiveness of iron supplementation are needed.


References:
Chermesh I et al. Failure of synbiotic 2000 to prevent postoperative recurrence of Crohn's disease. Dig Dis Sci. 2007 Feb;52(2):385-9. Epub 2007 Jan 9.

Kulnigg S and Gasche C. Systematic review: managing anaemia in Crohn's disease. Aliment Pharmacol Ther. 2006 Dec;24(11-12):1507-23.

Mach T. Clinical usefulness of probiotics in inflammatory bowel diseases. J physiology pharmacology 2006, 57, Suppl 9, 23-33.

Rachmilewitz D. et al. Toll R-9 Signaling Mediates the Anti-inflammatory Effect of Probiotics in Experimental Colitis. Gastroenterology 122:1428, 2002.

Richard F. and A. Logan. Inflammatory bowel disease incidence: up, down or unchanged? Gut 1998;42;309-311

Sinnott B.P and Licat A.A. Assessment of bone and mineral metabolism in inflammatory bowel disease: case series and review. Endocr Pract. 2006 Nov-Dec;12(6):622-9.

Yilmaz S. et al. The prevalence of ocular involvement in patients with inflammatory bowel disease. Int J Colorectal Dis. 2007 Jan 30;

For further reading visit also:
Lashner B.A. et al. True or False? The Hygiene Hypothesis for Crohn's Disease. Am J Gastroenterol 2006;101:1003–1004.
Böhm S.K. and Kruis W. Probiotics - Do they help to control intestinal inflammation? Ann. N.Y. Acad. Sci. 1072: 339–350 (2006)
Adler E.M. Focus Issue: Going for the Gut. Sci. STKE 2005 (277), eg4(2004)