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Chloe Terciolo,1,2 Michel Dapoigny,3 Frederic Andre4 1INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; 2Aix-Marseille Université, INSERM, UMR 911, CRO2, Marseille, France; 3Médecine Digestive, CHU Estaing, CHU Clermont-Ferrand, Université Clermont Auvergne, INSERM UMR 1107, Neuro-Dol, Clermont-Ferrand, France; 4Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc scientifique et technologique de Luminy, Marseille, France Abstract: Intestinal 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. Keywords: Saccharomyces boulardii CNCM I-745, apical junctional complex, leaky gut syndrome, intestinal barrier function, intestinal permeability, tight junctions

Background Short-chain fructooligosaccharides (sc FOS) have beneficial effects in subjects with minor digestive complaints, but the potential mechanisms involved have not been elucidated. The aim of the study was to evaluate changes in rectal sensitivity related to the clinical effects of sc FOS in a selected group of patients with irritable bowel syndrome ( IBS) and rectal hypersensitivity. Methods In 79 IBS patients (defined by Rome III criteria) with rectal hypersensitivity (defined as discomfort threshold ≤44 g) a parallel, placebo-controlled, randomized, and double-blind study was performed to assess the effects of dietary supplementation (5 g d−1) with sc FOS vs placebo for 4 weeks on rectal sensitivity (primary outcome: tolerance to increasing wall tension applied by a tensostat), clinical outcomes ( IBS, anxiety/depression and quality of life scores) and composition of fecal microbiota. Key Results Rectal discomfort threshold, and IBS and quality of life scores, significantly improved during treatment, but in a similar manner in both sc FOS and placebo groups; a post-hoc analysis showed that the effect of sc FOS on rectal sensitivity was more pronounced in constipation-predominant- IBS patients ( P=.051 vs placebo). Contrary with placebo, sc FOS significantly reduced anxiety scores and increased fecal Bifidobacteria ( P<.05 for both) without modifying other bacterial groups. Conclusions & Interfences The effect of sc FOS on anxiety may be related to modulation of the gut microbiota; demonstration of effects of sc FOS on rectal sensitivity may require higher doses and may depend on the IBS subgroup. [ABSTRACT FROM AUTHOR]

Aims This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio® and Lcr Restituo®) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35® in two animal models mimicking different features of irritable bowel syndrome ( IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins. Methods and Results The injection of 2,4,6-trinitrobenzenesulfonic acid ( TNBS) into the proximal colon as well as an acute partial restraint stress ( PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days. Conclusions This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation. Significance and Impact of the Study Two formulas of Lcr35® probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS. [ABSTRACT FROM AUTHOR]

Background Among the different mechanisms involved in irritable bowel syndrome ( IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. Methods This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav3.2- KO mice. Colonic sensitivity and Cav3.2 expression were studied after a low-dose treatment of dextran sodium sulfate ( DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav3.2 expression. Key results Wild-type, but not Cav3.2- KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav3.2 mRNA ( p = 0.04) was found in the colon of low-dose DSS-treated wild-type ( WT) mice compared to their controls. In human colonic biopsies, the Cav3.2 mRNA level was significantly higher in the IBS group compared to the control group ( p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. Conclusions & inferences This translational study supports the involvement of the calcium channels Cav3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels. [ABSTRACT FROM AUTHOR]