<p>Beneficial effects of <em>Saccharomyces boulardii</em> CNCM I-745 on clinical disorders associated with intestinal barrier disruption</p>

International audienceIntestinal barrier defects lead to "leaky gut syndrome", defined as an increase in intestinal permeability that allows the passage of luminal content into intestinal tissue and the bloodstream. Such a compromised intestinal barrier is the main factor underlying the pathogenesis of inflammatory bowel disease, but also commonly occurs in various systemic diseases such as viral infections and metabolic syndrome. The non-pathogenic yeast Saccharomyces boulardii CNCM I-745 has demonstrated its effectiveness as a probiotic in the prevention and treatment of antibiotic-associated, infectious and functional diarrhea. Via multiple mechanisms of action implicated in intestinal barrier function, S. boulardii has beneficial effects on altered intestinal microbiota and epithelial barrier defects in different pathologies. The well-studied probiotic yeast S. boulardii plays a crucial role in the preservation and/or restoration of intestinal barrier function in multiple disorders. This could be of major interest in diseases characterized by alterations in intestinal barrier function

Review article: Role of satiety hormones in anorexia induction by Trichothecene mycotoxins

International audienceThe trichothecenes, produced by Fusarium, contaminate animal feed and human food in all stages of production and lead to a large spectrum of adverse effects for animal and human health. An hallmark of trichothecenes toxicity is the onset of emesis followed by anorexia and food intake reduction in different animal species (mink, mice and pig). The modulation of emesis and anorexia can result from a direct action of trichothecenes in the brain or from an indirect action in the gastrointestinal tract. The direct action of trichothecenes involved specific brain areas such as nucleate tractus solitarius in the brainstem and the arcuate nuclei in the hypothalamus. Activation of these areas in the brain leads to the activation of specific neuronal populations containing anorexigenic factors (POMC and CART). The indirect action of trichothecenes in the gastrointestinal tract involved, by enteroendocrine cells, the secretion of several gut hormones such as cholecystokinin (CCK) and peptide YY (PYY) but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP) and 5-hydroxytryptamine (5-HT), which transmitted signals to the brain via the gut-brain axis. This review summarizes current knowledge on the effects of trichothecenes, especially deoxynivalenol, on emesis and anorexia and discusses the mechanisms underlying trichothecenes-induced food reduction

Molecular phenotyping of intestinal epithelial cells exposed to mycotoxins

National audienc

Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract.

Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis

Fumonisins at Doses below EU Regulatory Limits Induce Histological Alterations in Piglets

Fumonisins (FBs) are mycotoxins produced by Fusarium species that can contaminate human food and animal feed. Due to the harmful effects of FBs on animals, the European Union (EU) defined a recommendation of a maximum of 5 mg FBs (B1 + B2)/kg for complete feed for swine and 1 &micro;g FBs/kg body weight per day as the tolerable daily intake for humans. The aim of this study was to evaluate the toxicity of dietary exposure to low doses of FBs, including a dose below the EU regulatory limits. Four groups of 24 weaned castrated male piglets were exposed to feed containing 0, 3.7, 8.1, and 12.2 mg/kg of FBs for 28 days; the impact was measured by biochemical analysis and histopathological observations. Dietary exposure to FBs at a low dose (3.7 mg/kg of feed) significantly increased the plasma sphinganine-to-sphingosine ratio. FBs-contaminated diets led to histological modifications in the intestine, heart, lung, lymphoid organs, kidney, and liver. The histological alterations in the heart and the intestine appeared at the lowest dose of FBs-contaminated diet (3.7 mg/kg feed) and in the kidney at the intermediate dose (8.1 mg/kg feed). At the highest dose tested (12.2 mg/kg feed), all the organs displayed histological alterations. This dose also induced biochemical modifications indicative of kidney and liver alterations. In conclusion, our data indicate that FBs-contaminated diets at doses below the EU regulatory limit cause histological lesions in several organs. This study suggests that EU recommendations for the concentration of FBs in animal feed, especially for swine, are not sufficiently protective and that regulatory doses should be modified for better protection of animal health

CDX2 controls genes involved in the metabolism of 5-fluorouracil and is associated with reduced efficacy of chemotherapy in colorectal cancer

Most patients affected with colorectal cancers (CRC) are treated with 5-fluorouracil (5-FU)-based chemotherapy but its efficacy is often hampered by resistance mechanisms linked to tumor heterogeneity. A better understanding of the molecular determinants involved in chemoresistance is critical for precision medicine and therapeutic progress. Caudal type homeobox 2 (CDX2) is a master regulator of intestinal identity and acts as tumor suppressor in the colon. Here, using a translational approach, we examined the role of CDX2 in CRC chemoresistance. Unexpectedly, we discovered that the prognosis value of CDX2 for disease-free survival of patients affected with CRC is lost upon chemotherapy and that CDX2 expression enhances resistance of colon cancer cells towards 5-FU. At the molecular level, we found that CDX2 expression correlates with higher levels of genes regulating the bioavailability of 5-FU through efflux (ABCC11) and catabolism (DPYD) in patients affected with CRC and CRC cell lines. We further showed that CDX2 directly regulates the expression of ABCC11 and that the inhibition of ABCC11 improves 5-FU-sensitivity of CDX2-expressing colon cancer cells. Thus, this study illustrates how biological functions are hijacked in CRC cells and reveals the therapeutic interest of CDX2/ABCC11/DPYD to improve systemic chemotherapy in CRC

Saccharomyces boulardii CNCM I-745 Restores intestinal Barrier Integrity by Regulation of E-cadherin Recycling

International audienceAlteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease [IBD]. Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 [Sb], used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD

<em>Saccharomyces boulardii</em> Improves Intestinal Epithelial Cell Restitution by Inhibiting αvβ5 Integrin Activation State

<div><p>Intestinal epithelial cell damage is frequently seen in the mucosal lesions of infectious or inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the disappearance of inflammation and the repair of damaged epithelium. <em>Saccharomyces boulardii</em> (<em>Sb</em>, Biocodex) is a non-pathogenic yeast widely used as a preventive and therapeutic probiotic for the prevention and treatment of diarrhea and other gastrointestinal disorders. We recently showed that it enhances the repair of intestinal epithelium through activation of α2β1 integrin collagen receptors. In the present study, we demonstrated that α2β1 integrin is not the sole cell-extracellular matrix receptor involved during <em>Sb</em>-mediated intestinal restitution. Indeed, by using cell adhesion assays, we showed that <em>Sb</em> supernatant contains heat sensitive molecule(s), with a molecular weight higher than 9 kDa, which decreased αvβ5 integrin-mediated adhesion to vitronectin by competing with the integrin. Moreover, <em>Sb</em>-mediated changes in cell adhesion to vitronectin resulted in a reduction of the αvβ5signaling pathway. We used a monolayer wounding assay that mimics <em>in vivo</em> cell restitution to demonstrate that down-modulation of the αvβ5 integrin-vitronectin interaction is related to <em>Sb</em>-induced cell migration. We therefore postulated that <em>Sb</em> supernatant contains motogenic factors that enhance cell restitution through multiple pathways, including the dynamic fine regulation of αvβ5 integrin binding activity. This could be of major importance in diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases.</p> </div