title: The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.
abstract: BACKGROUND
  Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized.
  
  
  OBJECTIVE
  We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome.
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.|Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pigrau
authors.affiliation: Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: B K
authors.initials: BK
authors.lastname: Rodiño-Janeiro
authors.affiliation: Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Casado-Bedmar
authors.affiliation: Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Lobo
authors.affiliation: Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Vicario
authors.affiliation: Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Santos
authors.affiliation: Laboratory of Neuro-immuno-gastroenterology, Digestive Diseases Research Unit. Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Alonso-Cotoner
mesh_terms: D001921:Brain / Q000503:physiopathology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D008297:Male; D012737:Sex Factors; D013315:Stress, Psychological / Q000503:physiopathology*
keywords: brain-gut axis; gender; intestinal barrier; irritable bowel syndrome; microbiome; sex steroids; stress