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Article Dans Une Revue Neurogastroenterology & Motility Année : 2019

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

Résumé

Background: 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. Methods: Colonic tissue of BBDP-N and control (BBDR) rats at 50, 90, 110, 160, and 220 days (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 220 days and colonic sensitivity at 160 and 220 days by measuring the visceromotor response (VMR) to isobaric colorectal distensions. Keys results: Lamina propria eosinophil and mast cell infiltration and increased EPO activity were demonstrated from 90 days onward. Increased permeability and myenteric ganglionitis were observed in the oldest BBDP-N rats. At 220 days, the VMR was significantly increased suggesting colonic hypersensitivity. At the same age, increased anxiety-like behavior was observed. Conclusion and inferences: 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.
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Dates et versions

hal-04326848 , version 1 (06-12-2023)

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Mathieu Meleine, Alison Accarie, Lucas Wauters, Joran Toth, Guillaume Gourcerol, et al.. Colonic hypersensitivity and low‐grade inflammation in a spontaneous animal model for functional gastrointestinal disorders. Neurogastroenterology & Motility, 2019, 31 (7), pp.e13614. ⟨10.1111/nmo.13614⟩. ⟨hal-04326848⟩
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