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Colonic hypersensitivity and low-grade inflammation in a spontaneous animal model for functional gastrointestinal disorders.
Neurogastroenterol Motil 2019; 31(7):e13614NM

Abstract

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.

Authors+Show Affiliations

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium. Inserm UMR 1073, Institute for Innovation and Biomedical Research, Rouen University, Rouen, France.Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.Inserm UMR 1073, Institute for Innovation and Biomedical Research, Rouen University, Rouen, France.Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31069897

Citation

Meleine, Mathieu, et al. "Colonic Hypersensitivity and Low-grade Inflammation in a Spontaneous Animal Model for Functional Gastrointestinal Disorders." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 31, no. 7, 2019, pp. e13614.
Meleine M, Accarie A, Wauters L, et al. Colonic hypersensitivity and low-grade inflammation in a spontaneous animal model for functional gastrointestinal disorders. Neurogastroenterol Motil. 2019;31(7):e13614.
Meleine, M., Accarie, A., Wauters, L., Toth, J., Gourcerol, G., Tack, J., ... Vanuytsel, T. (2019). Colonic hypersensitivity and low-grade inflammation in a spontaneous animal model for functional gastrointestinal disorders. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 31(7), pp. e13614. doi:10.1111/nmo.13614.
Meleine M, et al. Colonic Hypersensitivity and Low-grade Inflammation in a Spontaneous Animal Model for Functional Gastrointestinal Disorders. Neurogastroenterol Motil. 2019;31(7):e13614. PubMed PMID: 31069897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Colonic hypersensitivity and low-grade inflammation in a spontaneous animal model for functional gastrointestinal disorders. AU - Meleine,Mathieu, AU - Accarie,Alison, AU - Wauters,Lucas, AU - Toth,Joran, AU - Gourcerol,Guillaume, AU - Tack,Jan, AU - Farré,Ricard, AU - Vanuytsel,Tim, Y1 - 2019/05/08/ PY - 2019/02/24/received PY - 2019/04/03/revised PY - 2019/04/16/accepted PY - 2019/5/10/pubmed PY - 2019/5/10/medline PY - 2019/5/10/entrez KW - BioBreeding rat KW - functional gastrointestinal disorder KW - intestinal permeability KW - visceral hypersensitivity SP - e13614 EP - e13614 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. VL - 31 IS - 7 N2 - 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. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/31069897/Colonic_hypersensitivity_and_low_grade_inflammation_in_a_spontaneous_animal_model_for_functional_gastrointestinal_disorders_ L2 - https://doi.org/10.1111/nmo.13614 DB - PRIME DP - Unbound Medicine ER -