Factors affecting outcomes in Crohn's disease over 15 years

International audienc

Rotavirus-Like Particles: A Novel Nanocarrier for the Gut

The delivery of bioactive molecules directly to damaged tissues represents a technological challenge. We propose here a new system based on virus-like particles (VLP) from rotavirus, with a marked tropism for the gut to deliver bio-active molecules to intestinal cells. For this, nonreplicative VLP nanoparticles were constructed using a baculovirus expression system and used to deliver an exogenous biomolecule, the green fluorescent protein (GFP), into either MA104 cells or intestinal cells from healthy and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice. Our results show that expression of rotavirus capsid proteins in baculovirus led to the auto assembly of VLP that display similar properties to rotavirus. In vitro experiments showed that VLP were able to enter into MA104 cells and deliver the reporter protein. Intragastric administration of fluorescent VLP in healthy and TNBS-treated mice resulted in the detection of GFP and viral proteins in intestinal samples. Our results demonstrate an efficient entry of non-replicative rotavirus VLP into the epithelial cell line MA104 and provide the first in vivo evidence of the potential of these nanoparticles as a promising safe candidate for drug delivery to intestinal cells

Fungal microbiota dysbiosis in IBD.

International audienceThe bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis

Saccharomyces boulardii CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers

Saccharomyces boulardii CNCM I-745 (SB) is a probiotic yeast used to lower the incidence of antibiotic-associated Clostridium difficile (C. difficile) infection, though its mechanism of action remains unclear. Cholic acid is a primary bile acid, which triggers the germination and promotes the growth of C. difficile. The intestinal microbiota transforms primary into secondary bile acids. This study examined (1) the antimicrobial-induced alteration of fecal bile acid content, and (2) whether the concomitant administration of SB influences this transformation. This is an ancillary work from a randomized study, which revealed that SB modulates fecal microbiota dysbiosis during antibiotic treatment. Healthy subjects were randomly assigned to (1) SB only, (2) amoxicillin-clavulanate (AC), (3) SB plus AC, or (4) no treatment. We analyzed fecal concentrations of BA by high performance liquid chromatography/tandem mass spectrometry. Compared to the untreated or the SB-treated groups, AC decreased the percentage of fecal secondary BA significantly (days 3 and 7). When SB and AC were administered concomitantly, this decrease in secondary BA was no longer significant. Following treatment with AC, a significant peak of fecal CA was measured on days 3 and 7, which was prevented by the concomitant administration of SB. AC administered to healthy volunteers altered the microbial transformation of primary BA, decreased secondary BA, and increased CA. The latter was prevented by the concomitant administration of SB and AC, suggesting a potent mechanism protection conferred by SB against post-antimicrobial C. difficile infection.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01473368

Microbial Dysbiosis in Colorectal Cancer (CRC) Patients

The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis

Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and Controls

Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

peer reviewe

Etude de la microflore digestive au cours de la maladie de Crohn par une approche moléculaire ciblant les ARNr 16S

La maladie de Crohn (MC) est une maladie de cause inconnue, se caractérisant par une inflammation focale du tube digestif De nombreux arguments incriminent la microflore dans sa pathogénie. Nous avons étudié la microflore fécale et muqueuse a au cours de la MC par des méthodes indépendantes de la culture: composition en groupes phylogénétiques par hybridation quantitative en dot-blot, analyse comparée de la biodiversité d'espèces dominantes par électrophorèse dénaturante en gradient de température et analyse de la microflore dominante fécale par la technique de l'inventaire moléculaire. Nos résultats sont concordants avec une augmentation des entérobactéries, une diminution des bifidobactéries et la présence de bactéries inhabituelles en dominance au cours de la MC par rapport au témoins. La microflore associée aux muqueuses, différente de la microflore fécale, paraissait stable chez un même individu de l'iléon au rectum quelque soit le statut clinique (MC, sujets sains). Au cours d'une poussée de MC chez un individu, les microflores dominantes associées aux muqueuses en zone ulcérée et non ulcérée étaient similairesThe cause of Crohn's Disease (CD), a focal inflammatory bowel disease, remains unknown. Several lines of evidence support the role of the microflora in its pathogenesis. We have studied fecal and mucosa-associated microflora during CD using culure-independant techniques: quantitative dot-blot hybridization for the composition in phylogenetic groups, temporal temperature gradient gel electrophoresis for comparison of the bacterial biodiversity and molecular inventory technique for the dominant species distribution. Our results are consistent with an increase in Enterobateria, a decrease in Bifidobacteria and the finding of unusual dominant species in fecal samples of CD compared with controls. Mucosa-associated microflora differed from fecal microflora and appeared stable from ileum to rectum in a same individual irrespective of his clinical status (CD or controls). During active CD, microflora associated with mucosal ulcerations was similar to microflora. associated with adjacent non ulcerated mucosaCHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Etude de la flore fécale chez l'homme atteint de maladie de Crohn par une approche moléculaire ciblant les ARNr 16S

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF