https://www.gastrojournal.org/article/S0016-5085(98)70381-6/pdf

Inflammatory bowel disease: Etiology and pathogenesis

IBD is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities: Crohn's disease and ulcerative colitis. Although Crohn's disease and ulcerative colitis have historically been studied together because they share common features (such as symptoms, structural damage and therapy), it is now clear that they represent two distinct pathophysiological entities. Both Crohn's disease and ulcerative colitis are associated with multiple pathogenic factors including environmental changes, an array of susceptibility gene variants, a qualitatively and quantitatively abnormal gut microbiota and a broadly dysregulated immune response. In spite of this realization and the identification of seemingly pertinent environmental, genetic, microbial and immune factors, a full understanding of IBD pathogenesis is still out of reach and, consequently, treatment is far from optimal. An important reason for this unsatisfactory situation is the currently limited comprehension of what are the truly relevant components of IBD immunopathogenesis. This article will comprehensively review current knowledge of the classic immune components and will expand the concept of IBD immunopathogenesis to include various cells, mediators and pathways that have not been traditionally associated with disease mechanisms, but that profoundly affect the overall intestinal inflammatory process.

Immunopathogenesis of IBD: current state of the art

A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host-microbial relationships relevant to human disease and amenable to therapeutic interventions.

Gut microbiota and IBD: causation or correlation?

Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes

Background—Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease. 
Aims—To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease. 
Methods—Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively. 
Results—The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement. 
Conclusion—ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease. 



Keywords: Crohn's disease; ulcerative colitis; antineutrophil cytoplasmic autoantibodies; anti-Saccharomyces cerevisiae mannan antibodies

https://gut.bmj.com/content/gutjnl/42/6/788.full.pdf

Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role

Comparaison de 55 cas de maladie de Crohn, 40 de colite ulcerative et 30 temoins normaux. Les titres d'anticorps IgG et IgA contre Saccharomyces cerevisiae sont significativement eleves dans la maladie de Crohn, non dans la colite ulcerative

https://www.bmj.com/content/bmj/297/6656/1105.full.pdf

Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease.

IgG serum antibody was measured by ELISA in patients with Crohn's disease (15), ulcerative colitis (15), and in normal controls (15) to 12 strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and to the two major serotypes of the commensal yeast Candida albicans. Antibody to 11 of the 12 strains of S cerevisiae was raised in patients with Crohn's disease but not in patients with ulcerative colitis when compared with controls (p less than 0.001). The pattern of antibody response to these 11 strains was variable, however, suggesting the likelihood of antigenic heterogeneity within the species. Antibody to C albicans was not significantly different in patient and control groups. The specificity of this unusual antibody response in Crohn's disease for S cerevisiae suggests that it is not simply the result of a generalised increase in intestinal permeability. Furthermore, because brewing and baking strains detected the response, the relevant antigen(s) are presumably common in the diet. Hypersensitivity to dietary antigens may be involved in the pathogenesis of Crohn's disease, and the role of S cerevisiae requires further investigation.

https://gut.bmj.com/content/gutjnl/31/5/536.full.pdf

Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease.

The effect of dietary yeast on the activity of stable Crohn's disease was assessed in 19 patients. During the 1st month patients continued their usual diet (base-line period), but during the next 2 months dietary yeast was excluded except that during 1 month patients took baker's yeast capsules while for the other month they took placebo capsules. The patients' mean Pettit Crohn's disease activity index (CDAI) while taking baker's yeast (mean, 107.9; SE, 6.1) was significantly greater than during yeast exclusion (mean, 102.1; SE, 5.7; p less than 0.05). The mean of each patient's maximum CDAI during yeast exclusion (mean, 107.1; SE, 5.7) was significantly lower than those during the base-line (mean, 115.2; SE, 6.1; p less than 0.05) and baker's yeast inclusion periods (mean, 113.9; SE, 6.7; p less than 0.05). Patients with elevated yeast antibodies tended to develop a higher CDAI while receiving baker's yeast (13 of 15). These results suggest that dietary yeast may affect the activity of Crohn's disease.

The effect of dietary yeast on the activity of stable chronic Crohn's disease.

The antigenic heterogeneity of twelve strains of Saccharomyces cerevisiae and serovar A and B strains of Candida albicans was investigated by cross-absorption of serum antibodies from a patient with Crohn's disease. On the basis of common antibody absorption patterns, eleven of the yeast strains were divided into Group 1 (five S. cerevisiae), Group 2 (two C. albicans, one S. cerevisiae) and Group 3 (three S. cerevisiae). The remaining three S. cerevisiae strains (Group 4) showed unique absorption patterns. The antigenic relationship between S. cerevisiae and C. albicans was further studied by cross-absorption of sera from eight patients with Crohn's disease. This confirmed a limited degree of cross-reaction between most strains of S. cerevisiae and C. albicans, but C. albicans serovar B significantly absorbed antibodies to more S. cerevisiae strains than did C. albicans serovar A. The results demonstrate considerable antigenic heterogeneity of S. cerevisiae and suggest that the elevated serum antibody levels to S. cerevisiae found in Crohn's disease are directed against multiple antigens.

Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognised by serum antibodies from patients with Crohn's disease.

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https://gut.bmj.com/content/gutjnl/30/3/422.1.full.pdf

H. McKenzie

Papers

Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease.

Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease.

The effect of dietary yeast on the activity of stable chronic Crohn's disease.

Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognised by serum antibodies from patients with Crohn's disease.

Bowel rest and nutritional support in the management of Crohn's disease.