Reduction of faecal immunochemical test false-positive results using a signature based on faecal bacterial markers.

BACKGROUND: Colorectal cancer is the second commonest cause of cancer mortality. Some countries are implementing colorectal cancer screening to detect lesions at an early stage using non-invasive tools like the faecal immunochemical test. Despite affordability, this test shows a low sensitivity for precancerous lesions and a low positive predictive value for colorectal cancer, resulting in a high false-positive rate. AIM: To develop a new, non-invasive colorectal cancer screening tool based on bacterial faecal biomarkers, which in combination with the faecal immunochemical test, could allow a reduction in the false-positive rate. This tool is called risk assessment of intestinal disease for colorectal cancer (RAID-CRC). METHODS: We performed both the faecal immunochemical test and the bacterial markers analysis (RAID-CRC test) in stool samples from individuals with normal colonoscopy (167), non-advanced adenomas (88), advanced adenomas (30) and colorectal cancer (48). All the participants showed colorectal cancer-associated symptoms. RESULTS: Performance of the faecal immunochemical test for advanced neoplasia (ie advanced adenoma and colorectal cancer) was determined by using the cut-off value established in Catalonia (20 µg haemoglobin/g of faeces) for a population-based screening approach. Sensitivity and specificity values of 83% and 80%, respectively, and positive and negative predictive values of 56% and 94%, respectively, were obtained. When both the immunological and the biological analysis were combined, the corresponding values were 80% and 90% for sensitivity and specificity, respectively, and 70% and 94% for positive and negative predictive values, respectively, resulting in a 50% reduction of the false-positive rate. CONCLUSIONS: RAID-CRC test allows a substantial reduction in the faecal immunochemical test false-positive results (50%) in a symptomatic population. Further validation is indicated in a colorectal cancer-screening scenario.

Anti-tumour Necrosis Factor Treatment with Adalimumab Induces Changes in the Microbiota of Crohn's Disease.

BACKGROUND: The composition of the intestinal microbiota is altered in Crohn's disease [CD] patients. The objective of this study was to evaluate the qualitative and quantitative changes in the microbiota of CD patients in 3 months of treatment with adalimumab [ADA], and determine whether or not these changes are produced towards the recovery of the normal, healthy-like microbiota. METHODS: The microbiota composition, and the Faecalibacterium prausnitzii / Escherichia coli quantitative relationship as dysbiosis indicator, were studied at baseline [T0], one month [T1], and 3 months [T3] after starting treatment using a polymerase chain reaction-denaturing gradient gel electrophoresis [PCR-DGGE] of 16S rRNA gene fragments and quantitative PCR, respectively, in rectal mucosal biopsies from 15 CD patients and four healthy subjects. RESULTS: T0 and T3 fingerprints were different in all patients; whereas T1 and T3 presented similar patterns. Recovered phylogroups were Firmicutes [79.1%], Bacteroides [12.5%], and Actinobacteria [6.25%]. The prevalence of E. coli decreased during treatment. Relative E. coli loads in CD samples were significantly reduced at every analysed step [T1 and T3] [p < 0.005] whereas no significant changes were observed in relative F. prausnitzii counts. CONCLUSION: Treatment with ADA induces short-term changes in the microbiota composition which seem to parallel the partial recovery of the gut bacterial ecology, with recovery parameters tending to eubiosis recovery. The quantitative determination of dysbiosis-representative bacteria, such as E. coli, may provide a fast and reliable indicator of the healing state of the intestinal mucosa.