Active Crohnʼs disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora

Abstract

BACKGROUND: The intestinal microflora is important in the pathogenesis of inflammatory bowel disease (IBD). The impact of its spatial organization on health and disease is unknown. METHODS: We investigated sections of paraffin-embedded punched fecal cylinders. Fluctuations in spatial distribution of 11 bacterial groups were monitored in healthy subjects (n = 32), patients with IBD (n = 204), and other gastrointestinal diseases (n = 186) using fluorescence in situ hybridization (FISH). RESULTS: The microbial structure differed in patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy and disease controls. The profiles of CD and UC were distinctly opposite in 6 of 11 FISH probes used. Most prominent were a depletion of Faecalibacterium prausnitzii (Fprau<1 x 10(9)/mL) with a normal leukocyte count in CD and a massive increase of leukocytes in the fecal-mucus transition zone (>30 leukocytes/10(4) microm(2)) with high Fprau in patients with UC. These 2 features alone enabled the recognition of active CD (Crohn's Disease Activity Index [CDAI] >150) or UC (Clinical Activity Index [CAI] >3) with 79%/80% sensitivity and 98%/100% specificity. The mismatch in the sensitivity was mainly due to overlap between single IBD entities, and the specificity was exclusively due to the similarity of Crohn's and celiac disease. When inflammatory bowel disease (IBD) patients were pooled the sensitivity was 100% for severe disease, 84% for moderate activity, 72% for IBD with < or =12 months remission, and 24% for IBD with >12 months remission. CONCLUSIONS: The fecal flora is highly structured and spatially organized. Diagnosing IBD and monitoring disease activity can be performed based on analysis of punched fecal cylinders independent from the patient's complaints.