Abstract
BackgroundIn recent years, the gut microbiota has been found to provide an important link to the development of inflammatory bowel diseases (IBD) like ulcerative colitis (UC). Accordingly, inter-individual variation in the gut microbial community may be linked to inter-individual variation in the risk of IBD or other diseases. Further, the Terminal Restriction Fragment Length Polymorphism (T-RFLP) is a molecular biology technique for profiling bacterial species in faecal samples. This study was to evaluate a biomarker based on intestinal microbiota.MethodsThe study subjects were 69 patients with UC together with 80 relatives as controls. Twenty-three patients had active UC (group I) and 46 had quiescent UC (group II). The later included 17 patients with mild inflammation in the large intestine (group IIa), 29 without inflammation (group IIb). The patients’ relatives were consanguineous (group III, n = 47), and non-consanguineous (group IV, n = 33). Faecal samples were obtained from all subjects for the investigation of intestinal microbiota by applying the T-RFLP method. The Discriminant analysis of operational-taxonomic-unit (OTU) on T-RFLP fingerprints was performed. The Canonical Discriminant Function Coefficient (Df) for each OTU was calculated. The individual OTUs were multiplied by the Df value, and the sum was termed the Discriminant Score (Ds).ResultsThe Ds decreased thus: group I > group IIa > group IIb > group III > group IV. Significant difference was calculated for group I vs group IV (P < 0.01), group I vs group IIb (P < 0.05), group I vs group III (P < 0.01), group IIa vs IV (P < 0.01), group IIb vs group IV (P < 0.01), group III vs group IV (P < 0.01), indicating a strong association between gut microbial species and the development of UC.ConclusionsIn this study, the Ds related to UC, or otherwise absence of UC in the five groups. Potentially, Ds may become a clinically relevant biomarker of disease activity in UC. To our knowledge, this is the first application of the Ds to the study of microbiota in UC patients, consanguineous and non-consanguineous relatives.Trial registrationClinical trial No: UMIN 000004123.
Highlights
In recent years, the gut microbiota has been found to provide an important link to the development of inflammatory bowel diseases (IBD) like ulcerative colitis (UC)
It was thought that the difference of intestinal microbiota between patients with active UC and nonconsanguineous relatives might be greater than between any other two groups
The knowledge that the intestinal microbiota in patients with UC is a major factor in the aetiology of this condition is supported by animal models of colitis, reporting that the development of UC-like colitis did not occur under bacterial free conditions [14,15], but in the same setting, colitis occurred following introduction of gut bacteria from a UC patient [14]
Summary
The gut microbiota has been found to provide an important link to the development of inflammatory bowel diseases (IBD) like ulcerative colitis (UC). While it is understood that the presence of this microbiota is essential for the human health, this relationship may become unbalanced, resulting in diseases like UC and CD [2,3] Both clinical and experimental evidence suggest that IBD fare-ups are triggered by a combined loss of the so-called intestinal barrier function and a dysregulated immune response to the intestinal microbiota [2,3,4,5,6,7,8,9,10,11,12]. In animal models of IBD, experimental colitis is reported not to occur under bacteria-free condition [6,13,14] This seems paradoxical as the human intestinal bacteria are known to metabolize compounds that might be essential for human nutrition [15,16]. Probiotics, which change the composition of intestinal microbiota have shown efficacy in patients with IBD [3, 17,18,19,20,21,22], suggesting that among the vast species of bacteria which are found in the human intestine, there are both pro-inflammatory [23,24], as well as protective strains [17]
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