Abstract

BackgroundWe evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure.MethodsMice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1β, IL-10 and IL-4.ResultsS. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100β protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins.ConclusionsS. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome.

Highlights

  • Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that significantly affects patient quality of life [1,2]

  • We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure

  • S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome

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Summary

Introduction

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that significantly affects patient quality of life [1,2]. It is the most commonly diagnosed gastrointestinal condition affecting up to 10−15% of the population in industrialized countries [2,3]. Neuroplasticity disorders of the enteric nervous system (ENS) have been described in functional and inflammatory bowel diseases [4]. Infiltrating CD3 lymphocytes have been detected in the myenteric plexus of patients with severe gastrointestinal motor disorders requiring surgical resection, such as gastroparesis, chronic intestinal pseudo-obstruction, and slow-transit constipation [6]. We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure

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