The distinct features of microbial 'dysbiosis' of Crohn's disease do not occur to the same extent in their unaffected, genetically linked kindred

Background/Aims: Studying the gut microbiota in unaffected relatives of people with Crohn’s disease (CD) may advance our understanding of the role of bacteria in disease aetiology. Methods: Faecal microbiota composition (16S rRNA gene sequencing), genetic functional capacity (shotgun metagenomics) and faecal short chain fatty acids (SCFA) were compared in unaffected adult relatives of CD children (CDR, n = 17) and adult healthy controls, unrelated to CD patients (HUC, n = 14). The microbiota characteristics of 19 CD children were used as a benchmark of CD ‘dysbiosis’. Results: The CDR microbiota was less diverse (p = 0.044) than that of the HUC group. Local contribution of β-diversity analysis showed no difference in community structure between the CDR and HUC groups. Twenty one of 1,243 (1.8%) operational taxonomic units discriminated CDR from HUC. The metagenomic functional capacity (p = 0.207) and SCFA concentration or pattern were similar between CDR and HUC (p>0.05 for all SCFA). None of the KEGG metabolic pathways were different between these two groups. Both of these groups (HUC and CDR) had a higher microbiota α-diversity (CDR, p = 0.026 and HUC, p<0.001) with a community structure (β-diversity) distinct from that of children with CD. Conclusions: While some alterations were observed, a distinct microbial ‘dysbiosis’, characteristic of CD patients, was not observed in their unaffected, genetically linked kindred

Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans

Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan–antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. We show that antibody avidity as a measure of antigenicity increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort

Alleviation of high fat diet-induced obesity by oligofructose in gnotobiotic mice is independent of presence of Bifidobacterium longum

SCOPE: Diet-induced obesity is associated with changes in the gut microbiota and low-grade inflammation. Oligofructose was reported to ameliorate high fat diet-induced metabolic disorders in mice by restoring the number of intestinal bifidobacteria. However, this has not been experimentally demonstrated. METHODS AND RESULTS: We fed conventional mice, germfree mice, mice associated with a simplified human gut microbiota composed of eight bacterial species including Bifidobacterium longum (SIHUMI), and mice associated with SIHUMI without B. longum a low fat diet (LFD), a high fat diet (HFD), or a HFD containing 10% oligofructose (HFD + OFS) for five weeks. We assessed body composition, bacterial cell numbers and metabolites, markers of inflammation, and gut permeability. Conventional mice fed HFD or HFD + OFS did not differ in body weight gain and glucose tolerance. The gnotobiotic mouse groups fed LFD or HFD + OFS gained less body weight and body fat, and displayed an improved glucose tolerance compared with mice fed HFD. These differences were not affected by the presence of B. longum. Mice fed HFD showed no signs of inflammation or increased intestinal permeability. CONCLUSION: The ability of oligofructose to reduce obesity and to improve glucose tolerance in gnotobiotic mice fed HFD was independent of the presence of B. longum

Role of Faecalibacterium prausnitzii in Crohnʼs Disease

No abstract available

Subject characteristics.

<p>Subject characteristics.</p

Microbiota composition and functionality characteristics of unaffected relatives of children with Crohn’s disease, their unaffected relatives and healthy controls with no familial history of IBD.

<p>A) Non-metric multidimensional scaling (NMDS) plot using Bray-Curtis dissimilarity index which considers bacterial taxon presence and abundance. B) Non-metric multidimensional scaling (NMDS) plot using Unifrac phylogenetic distances which takes into account the phylogenetic distances (relatedness) of the bacterial taxa, without accounting for their abundance; The ellipses in A and B represent the 95% confidence intervals based on the standard errors of the average of the axis scores for each group using the ordiellipse function of the R's vegan package C) Local contribution of β-diversity (LCBD) analysis which considers the contribution of each sample to the total OTU β-diversity, calculated from all study samples together (% of total community dispersion); D) Shannon α-diversity (expressed in richness equivalents) based on operational taxonomic unit assignments (OTU) (p = 0.039 when accounting for the genetic relatedness of the participants in the CDR and CD group using paired data analysis); E) Diversity of KEGG metabolic pathways based on metagenomics sequencing (p = 0.127 when accounting for the genetic relatedness of the participants in the CDR and CD group using paired data analysis); F) Faecal short chain fatty acids (μmol/g and % of total SCFA); The size of the dot is proportional to the concentration of faecal calprotectin; CD: Children with Crohn’s disease, CDR: Unaffected blood relatives of children with Crohn’s disease, HUC: Healthy controls unrelated to patients with inflammatory bowel disease.</p

Log-relative abundances of OTUs which differentiated unaffected relatives of children with Crohn’s disease and healthy controls with no familial history of the disease.

<p>Taxonomic classification is given at the highest level of phylogenetic resolution. Within red box frames those OTUs which were identical to the ones which differed between children with CD and healthy paediatric controls in a previous study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172605#pone.0172605.ref003" target="_blank">3</a>]^. CDR: Unaffected blood relatives of children with Crohn’s disease, HUC: Healthy controls unrelated to patients with inflammatory bowel disease.</p