Reduced Interstitial Cells of Cajal and Increased Intraepithelial Lymphocytes Are Associated With Development of Small Intestinal Bacterial Overgrowth in Post-Infectious IBS Mouse Model

Scand J Gastroenterol. 2017 Oct;52(10):1065-1071. doi: 10.1080/00365521.2017.1342141. Epub 2017 Jul 5.

Abstract

Objective: Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model.

Materials and methods: NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined.

Results: PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group.

Conclusions: Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Keywords: Small intestinal bacterial overgrowth; interstitial cells of Cajal; intraepithelial lymphocyte; irritable bowel syndrome.

MeSH terms

  • Animals
  • Blind Loop Syndrome / immunology
  • Blind Loop Syndrome / parasitology
  • Blind Loop Syndrome / pathology*
  • Disease Models, Animal
  • Ileum / metabolism
  • Ileum / microbiology
  • Ileum / pathology*
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Interstitial Cells of Cajal / pathology*
  • Intestinal Mucosa / pathology*
  • Irritable Bowel Syndrome / immunology
  • Irritable Bowel Syndrome / parasitology
  • Irritable Bowel Syndrome / pathology*
  • Jejunum / microbiology
  • Lymphocyte Count
  • Male
  • Mice
  • Toll-Like Receptor 4 / metabolism
  • Trichinella spiralis
  • Trichinellosis / complications

Substances

  • IL10 protein, mouse
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • interleukin-6, mouse
  • Interleukin-10