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Wrzosek L.,French National Institute for Agricultural Research | Wrzosek L.,Agro ParisTech | Wrzosek L.,Commensal and Probiotics Host Interactions Laboratory | Miquel S.,French National Institute for Agricultural Research | And 29 more authors.
BMC Biology | Year: 2013

Background: The intestinal mucus layer plays a key role in the maintenance of host-microbiota homeostasis. To document the crosstalk between the host and microbiota, we used gnotobiotic models to study the influence of two major commensal bacteria, Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii, on this intestinal mucus layer. B. thetaiotaomicron is known to use polysaccharides from mucus, but its effect on goblet cells has not been addressed so far. F. prausnitzii is of particular physiological importance because it can be considered as a sensor and a marker of human health. We determined whether B. thetaiotaomicron affected goblet cell differentiation, mucin synthesis and glycosylation in the colonic epithelium. We then investigated how F. prausnitzii influenced the colonic epithelial responses to B. thetaiotaomicron.Results: B. thetaiotaomicron, an acetate producer, increased goblet cell differentiation, expression of mucus-related genes and the ratio of sialylated to sulfated mucins in mono-associated rats. B. thetaiotaomicron, therefore, stimulates the secretory lineage, favoring mucus production. When B. thetaiotaomicron was associated with F. prausnitzii, an acetate consumer and a butyrate producer, the effects on goblet cells and mucin glycosylation were diminished. F. prausnitzii, by attenuating the effects of B. thetaiotaomicron on mucus, may help the epithelium to maintain appropriate proportions of different cell types of the secretory lineage. Using a mucus-producing cell line, we showed that acetate up-regulated KLF4, a transcription factor involved in goblet cell differentiation.Conclusions: B. thetaiotaomicron and F. prausnitzii, which are metabolically complementary, modulate, in vivo, the intestinal mucus barrier by modifying goblet cells and mucin glycosylation. Our study reveals the importance of the balance between two main commensal bacteria in maintaining colonic epithelial homeostasis via their respective effects on mucus. © 2013 Wrzosek et al.; licensee BioMed Central Ltd.

Deschemin J.-C.,French Institute of Health and Medical Research | Deschemin J.-C.,French National Center for Scientific Research | Deschemin J.-C.,University of Paris Descartes | Deschemin J.-C.,Laboratory of Excellence GR Ex | And 31 more authors.
FASEB Journal | Year: 2016

The amount of iron in the diet directly influences the composition of the microbiota. Inversely, the effects of the microbiota on iron homeostasis have been little studied. So, we investigate whether the microbiota itself may alter host iron sensing. Duodenal cytochrome b and divalent metal transporter 1, involved in apical iron uptake, are 8- and 10-fold, respectively, more abundant in the duodenum of germ-free (GF) mice than in mice colonized with a microbiota. In contrast, the luminal exporter ferroportin is 2-fold less abundant in GF. The overall signature of microbiota on iron-related proteins is similar in the colon. The colonization does not modify systemic parameters as plasma transferrin saturation (20%), plasma ferritin (150 ng/L), and liver (85 μg/g) iron load. Commensal organisms (Bacteroides thetaiotaomicron VPI-5482 and Faecalibacterium prausnitzii A2-165) and a probiotic strain (Streptococcus thermophilus LMD-9) led to up to 12-fold induction of ferritin in colon. Our data suggest that the intestinal cells of GF mice are depleted of iron and that following colonization, the epithelial cells favor iron storage. This study is the first to demonstrate that gut microbes induce a specific iron-related protein signature, highlighting new aspects of the crosstalk between the microbiota and the intestinal epithelium. © FASEB.

Delvincourt M.,Assistance Publique Hopitaux Of Paris And Paris Vi University | Lopez A.,University of Lorraine | Pillet S.,Saint Etienne Hospital | Pillet S.,Jean Monnet University | And 13 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014

Summary Background Consequences of latent cytomegalovirus (CMV) infection reactivation on inflammatory bowel disease (IBD) flare, as a flare-worsening factor or simple bystander, are debated. Impact of anti-viral treatment on IBD course is poorly known. Aim To assess the impact of CMV reactivation on patients hospitalised for IBD flare and the effect of anti-viral treatment on IBD flare in patients with CMV reactivation. Methods First, a population of UC patients from Saint-Antoine hospital, in flare with positive blood CMV PCR without anti-viral treatment (n = 26), were compared to matched patients with negative blood CMV PCR in a case-control study. Secondly, a total of 110 hospitalisations between October 2003 and May 2012 for IBD flare-up with CMV reactivation (80 diagnosed on blood PCR, 33 on tissue PCR) were identified in three French referral centres. Evolution following CMV reactivation diagnosis was compared between patients receiving anti-viral treatment and those who did not. Results In the case-control study, no differences were observed between the two groups regarding length of hospital stay and colectomy rate. Comparing treated and untreated patients, no differences were observed at inclusion regarding age, gender, IBD type, immunosuppressant, CRP and haemoglobin level. No differences were observed regarding CRP level decrease at 10 days and colectomy rate at 3 months. Anti-viral treatment was associated with lower serum albumin level at inclusion and longer hospitalisation. Conclusions CMV reactivation does not appear to alter the course of IBD flare. CMV treatment does not seem to impact the course of IBD. These results should be confirmed prospectively. © 2014 John Wiley & Sons Ltd.

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