J Neurogastroenterol Motil.  2015 Apr;21(2):222-235. 10.5056/jnm14136.

Lipopolysaccharides Facilitate Colonic Motor Alterations Associated to the Sensitization to a Luminal Antigen in Rats

Affiliations
  • 1Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Spain. vicente.martinez@uab.es
  • 2Instituto de Neurociencias, Universitat Autonoma de Barcelona, Spain.
  • 3Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.

Abstract

BACKGROUND/AIMS
Enteric dysbiosis is a risk factor for dietary proteins-associated intestinal alterations, contributing to the development of food allergies and the symptomatology of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS). We explored if a dysbiotic-like state, simulated by intraperitoneal administration of bacterial lipopolysaccharides (LPS), facilitates the sensitization to a luminal antigen, ovalbumin (OVA), in rats.
METHODS
Rats were exposed to oral OVA for 1 week, alone or with LPS. Thereafter, colonic histology, goblet cell density, mucosal eosinophils and mucosal mast cell (MMC) and connective tissue mast cell (CTMC) were evaluated. Colonic expression (real-time quantitative polymerase chain reaction) of interleukins, IFN-alpha1 and integrins was assessed to determine local immune responses. Luminal and wall adhered microbiota were characterized by fluorescence in situ hybridization. Colonic contractility (in vitro) served to assess functional changes associated to OVA and/or LPS.
RESULTS
Neither OVA nor LPS, alone or combined, lead to structural alterations, except for a reduced goblet cell density in OVA-LPS-treated rats. MMC density was unaffected, while CTMC counts increased within the submucosa of OVA-LPS-treated animals. Marginal immune activation (IFN-alpha1 up-regulation) was observed in OVA-LPS-treated rats. LPS induced a dysbiotic-like state characterized by decreased luminal bacterial counts, with a specific loss of clostridia. LPS facilitated Clostridium spp. wall adherence, an effect prevented by OVA. Colonic contractility was altered in OVA-LPS-treated animals, showing increased basal activity and enhanced motor responses to OVA.
CONCLUSIONS
Changes in gut microbiota and/or direct effects of LPS might enhance/facilitate local neuroimmune responses to food antigens leading to motor alterations similar to those observed in IBS.

Keyword

Food hypersensitivity; Gastrointestinal diseases; Irritable bowel syndrome; Microbiota; Ovalbumin

MeSH Terms

Animals
Bacterial Load
Clostridium
Colon*
Connective Tissue
Dysbiosis
Eosinophils
Fluorescence
Food Hypersensitivity
Gastrointestinal Diseases
Goblet Cells
In Situ Hybridization
Integrins
Interleukins
Irritable Bowel Syndrome
Lipopolysaccharides*
Mast Cells
Microbiota
Ovalbumin
Ovum
Phenobarbital*
Rats*
Risk Factors
Integrins
Interleukins
Lipopolysaccharides
Ovalbumin
Phenobarbital
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