Colonic hypersensitivity and low-grade inflammation in a spontaneous animal model for functional gastrointestinal disorders.

Abstract

A complex interplay between a failing intestinal barrier and low-grade inflammation leading to sensorimotor disturbances is an often-cited mechanism in the pathogenesis of functional gastrointestinal disorders (FGID). However, the cause-consequence relationship between these features has not been clearly established. We previously described jejunal alterations in the normoglycemic BB-rat (BBDP-N) model proposing this model as a suitable animal model to study FGID pathophysiology. The current study explores colonic permeability, inflammation, and sensitivity of the BB-rat. Colonic tissue of BBDP-N and control (BBDR) rats at 50, 90, 110, 160, and 220days (n≥7 per group) was used to assess intestinal permeability in Ussing chambers and inflammation, including infiltration by eosinophils, mast cells, and eosinophil peroxidase (EPO) activity. Anxiety-like symptoms were evaluated at 50, 90, and 220days and colonic sensitivity at 160 and 220days by measuring the visceromotor response (VMR) to isobaric colorectal distensions. Lamina propria eosinophil and mast cell infiltration and increased EPO activity were demonstrated from 90days onward. Increased permeability and myenteric ganglionitis were observed in the oldest BBDP-N rats. At 220days, the VMR was significantly increased suggesting colonic hypersensitivity. At the same age, increased anxiety-like behavior was observed. We demonstrated a lamina propria eosinophil and mast cell infiltration preceding visceral hypersensitivity in the colon of the BBDP-N rat, reminiscent of patients with FGID. These findings help elucidating pathogenetic pathways in FGID and further validate the BBDP-N rat as an attractive model to study pathophysiology and therapy of FGID.