The gut microbiota is implicated in the pathogenesis of Crohn's disease (CD). Exclusive enteral nutrition (EEN) is a successful treatment, but its mode of action remains unknown. This study assessed serial changes in the fecal microbiota milieu during EEN. Five fecal samples were collected from CD children: 4 during EEN (start, 15, 30, end EEN approximately 60 days) and the fifth on habitual diet. Two samples were collected from healthy control subjects. Fecal pH, bacterial metabolites, global microbial diversity abundance, composition stability, and quantitative changes of total and 7 major bacterial groups previously implicated in CD were measured. Overall, 68 samples were from 15 CD children and 40 from 21 control subjects. Fecal pH and total sulfide increased and butyric acid decreased during EEN (all P < 0.05). Global bacterial diversity abundance decreased (P < 0.05); a higher degree of microbiota composition stability was seen in control subjects than in CD children during EEN (at P ≤ 0.008). Faecalibacterium prausnitzii spp concentration significantly decreased after 30 days on EEN (P < 0.05). In patients who responded to EEN, the magnitude of the observed changes was greater and the concentration of Bacteroides/Prevotella group decreased (P < 0.05). All these changes reverted to pretreatment levels on free diet, and EEN microbiota diversity increased when the children returned to their free diet. EEN impacts on gut microbiota composition and changes fecal metabolic activity. It is difficult to infer a causative association between such changes and disease improvement, but the results do challenge the current perception of a protective role for F. prausnitzii in CD.

Background And Aims It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). Methods We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. Results Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. Conclusions Although several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

The cytoskeletal protein vimentin plays a key role in positioning of organelles within the cytosol and has been linked to the regulation of numerous cellular processes including autophagy, however, how vimentin regulates autophagy remains relatively unexplored. Here we report that inhibition of vimentin using the steroidal lactone Withaferin A (WFA) causes vimentin to aggregate, and this is associated with the relocalisation of organelles including autophagosomes and lysosomes from the cytosol to a juxtanuclear location. Vimentin inhibition causes autophagosomes to accumulate, and we demonstrate this results from modulation of mechanistic target of rapamycin (mTORC1) activity, and disruption of autophagosome-lysosome fusion. We suggest that vimentin plays a physiological role in autophagosome and lysosome positioning, thus identifying vimentin as a key factor in the regulation of mTORC1 and autophagy.

Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohn’s disease (CD) is elusive. Microscopic erosions over the ileal Peyer’s patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyer’s patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyer’s patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyer’s patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyer’s patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)