New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population

Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 μg/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs

Definition of a microbial signature as a predictor of endoscopic post-surgical recurrence in patients with Crohn’s disease

Background and aims: Although there are several effective drugs for the treatment of Crohn’s disease (CD), almost 70% of patients will require surgical resection during their lifetime. This procedure is not always curative, as endoscopic recurrence occurs in 65%–90% of patients in the first year after surgery. The aetiology of the recurrence is unknown; however, several studies have shown how the resident microbiota is modified after surgery. The aim of this study was to evaluate samples from patients with Crohn’s disease before and after an intestinal resection to determine whether there were differences in the abundance of different microbial markers, which may predict endoscopic recurrence at baseline.Methods: In this observational study, a stool sample was obtained from 25 patients with Crohn’s disease before undergoing surgery, recruited at three Catalan hospitals. From each sample, DNA was purified and the relative abundance of nine microbial markers was quantified using qPCR.Results: An algorithm composed of four microbial markers (E. coli, F. prausnitzii phylogroup I, Bacteroidetes, and Eubacteria) showed a sensitivity and specificity of 90.91% and 85.71%, respectively, and a positive and negative predictive value of 83.33% and 92.31%, respectively.Conclusion: A microbial signature to determine patients who will have post-surgical recurrence was identified. This tool might be very useful in daily clinical practice, allowing the scheduling of personalized therapy and enabling preventive treatment only in patients who really require it

Signatures bacterianes com a eines de diagnòstic diferencial i monitoratge de les malalties inflamatòries intestinals

Inflammatory Bowel Disease (IBD) is a group of immune-based pathologies that affect the digestive tract, causing chronic inflammatory diseases processes. In recent years, the microbial communities that inhabit the human intestine have been associated with different diseases, among which IBD stands out. Identifying microbiological signatures in faecal samples from patients with IBD and IBS could be useful to diagnose, monitor, and even predict therapeutic results. The study of the intestinal microbiota using faecal samples, is a simple and quick process. The methodology used for its study has been defined and optimized in this work. In this doctoral thesis, RAID-Dx, a non-invasive method capable of discriminating IBS from IBD with a sensitivity of 88.2% and a specificity of 94.1%, and RAID-Monitor, a non-invasive method capable of monitoring the endoscopic activity in IBD patients, were developed.La Malaltia Inflamatòria Intestinal (MII) és un grup de patologies de base immune que afecten al tracte digestiu, provocant processos inflamatoris crònics. Durant els últims anys, les comunitats microbianes que habiten l’intestí humà han estat relacionades amb un bon nombre de malalties, entre les que destaca la MII. La identificació de signatures microbiològiques en mostres fecals de pacients amb MII i SII podria ser útils per diagnosticar, monitoritzar i, fins i tot, predir-ne resultats terapèutics. L’anàlisi de la microbiota intestinal a partir d’una mostra fecal és un procés senzill i ràpid. La metodologia emprada per estudiar-la ha estat en part definida i optimitzada en aquest treball. A partir d’aquesta metodologia, s’ha desenvolupat el RAID-Dx, procediment no invasiu capaç de discriminar la SII de la MII amb una sensibilitat del 88,2% i una especificitat del 94,1% i també el RAID-Monitor, que permet monitoritzar l’activitat endoscòpica en pacients de MC i CU.Programa de Doctorat en Biologia Molecular, Biomedicina i Salu

Contribution to the knowledge of the distribution of Chaoborus species (Diptera: Chaoboridae) in the NE Iberian Peninsula, with notes on the spatial and temporal segregation among them

Phantom midges are characteristic inhabitants of standing waters and are well known for their diel migrations. Despite the extensive body of literature covering their ecology, there are still knowledge gaps with regards to the factors that determine their distribution. Furthermore, although spatial and temporal segregation patterns among chaoborids have long been reported, the prevalence of such patterns in shallow waters remains unclear. We investigated the distribution of Chaoborus species, as well as their spatial and temporal segregation and diel mesohabitat migration, in the NE Iberian Peninsula. We detected three Chaoborus species (C. crystallinus, C. pallidus and C. flavicans), with the latter being the most dominant, and co-occurrences among these species being very low. C. flavicans did not perform diel horizontal migrations, although in one of the ponds it showed high affinities to vegetated areas during both day- and night-time, similar to its potential predators. Therefore, although we did not observe the role of diel horizontal migrations as an antipredator mechanism in shallow water bodies, aquatic vegetation could confer refuge to the chaoborid larvae.Las larvas del género Chaoborus son unos habitantes típicos de aguas estancadas con unos patrones muy marcados de migración vertical diaria. Aunque existe una extensa bibliografía de su papel ecológico y biológico, existen aún algunos interrogantes en relación a su distribución. Además, aunque los patrones de segregación espacial y temporal en los caobóridos están bien documentados, en aguas someras siguen sin estar claros. Nuestro estudio se centra en la distribución de las especies del género Chaoborus en el NE de la Península Ibérica, su segregación espacial y temporal y las migraciones diarias entre mesohábitats. Se detectaron tres especies del género Chaoborus (C. crystallinus, C. pallidus y C. flavicans), siendo la última la más abundante, y unas coocurrencias entre estas especies muy bajas. C. flavicans no mostró ninguna migración diaria horizontal, aunque en una de las charcas presentó una afinidad mayor por las zonas vegetadas tanto de día como de noche, al igual que sus predadores potenciales. Por lo que, aunque no se observaron patrones de migración horizontal diaria como mecanismo antipredador en masas de agua someras, la vegetación acuática podría suponer un refugio para las larvas de Chaoborus

Contribution to the knowledge of the distribution of Chaoborus species (Diptera: Chaoboridae) in the NE Iberian Peninsula, with notes on the spatial and temporal segregation among them

Phantom midges are characteristic inhabitants of standing waters and are well known for their diel migrations. Despite theextensive body of literature covering their ecology, there are still knowledge gaps with regards to the factors that determinetheir distribution. Furthermore, although spatial and temporal segregation patterns among chaoborids have long been reported,the prevalence of such patterns in shallow waters remains unclear. We investigated the distribution of Chaoborus species, aswell as their spatial and temporal segregation and diel mesohabitat migration, in the NE Iberian Peninsula. We detected threeChaoborus species (C. crystallinus, C. pallidus and C. flavicans), with the latter being the most dominant, and co-occurrencesamong these species being very low. C. flavicans did not perform diel horizontal migrations, although in one of the pondsit showed high affinities to vegetated areas during both day- and night-time, similar to its potential predators. Therefore,although we did not observe the role of diel horizontal migrations as an antipredator mechanism in shallow water bodies,aquatic vegetation could confer refuge to the chaoborid larvaeLas larvas del género Chaoborus son unos habitantes típicos de aguas estancadas con unos patrones muy marcados de migraciónvertical diaria. Aunque existe una extensa bibliografía de su papel ecológico y biológico, existen aún algunos interrogantesen relación a su distribución. Además, aunque los patrones de segregación espacial y temporal en los caobóridos estánbien documentados, en aguas someras siguen sin estar claros. Nuestro estudio se centra en la distribución de las especies delgénero Chaoborus en el NE de la Península Ibérica, su segregación espacial y temporal y las migraciones diarias entre mesohábitats.Se detectaron tres especies del género Chaoborus (C. crystallinus, C. pallidus y C. flavicans), siendo la última la másabundante, y unas coocurrencias entre estas especies muy bajas. C. flavicans no mostró ninguna migración diaria horizontal,aunque en una de las charcas presentó una afinidad mayor por las zonas vegetadas tanto de día como de noche, al igual quesus predadores potenciales. Por lo que, aunque no se observaron patrones de migración horizontal diaria como mecanismoantipredador en masas de agua someras, la vegetación acuática podría suponer un refugio para las larvas de ChaoborusThis work was supported by the "Ministerio de Ciencia e Innovacion" (CGL2011-23907) and the Generalitat de Catalunya (ref. 2014 SGR 484