Environmental Science and Pollution Research

, Volume 25, Issue 23, pp 22529–22540 | Cite as

Use of a combination of in vitro models to investigate the impact of chlorpyrifos and inulin on the intestinal microbiota and the permeability of the intestinal mucosa

  • Marina Réquilé
  • Dubàn O. Gonzàlez Alvarez
  • Stéphane Delanaud
  • Larbi Rhazi
  • Véronique Bach
  • Flore Depeint
  • Hafida Khorsi-Cauet
Research Article


Dietary exposure to the organophosphorothionate pesticide chlorpyrifos (CPF) has been linked to dysbiosis of the gut microbiota. We therefore sought to investigate whether (i) CPF’s impact extends to the intestinal barrier and (ii) the prebiotic inulin could prevent such an effect. In vitro models mimicking the intestinal environment (the SHIME®) and the intestinal mucosa (Caco-2/TC7 cells) were exposed to CPF. After the SHIME® had been exposed to CPF and/or inulin, we assessed the system’s bacterial and metabolic profiles. Extracts from the SHIME®’s colon reactors were then transferred to Caco-2/TC7 cultures, and epithelial barrier integrity and function were assessed. We found that inulin co-treatment partially reversed CPF-induced dysbiosis and increased short-chain fatty acid production in the SHIME®. Furthermore, co-treatment impacted tight junction gene expression and inhibited pro-inflammatory signaling in the Caco-2/TC7 intestinal cell line. Whereas, an isolated in vitro assessment of CPF and inulin effects provides useful information on the mechanism of dysbiosis, combining two in vitro models increases the in vivo relevance.


Caco-2/TC7 Chlorpyrifos Inulin Dysbiosis Microbiota SHIME® 





Simulator of the Human Intestinal Microbial Ecosystem


complementary DNA




Toll-like receptor


transepithelial electrical resistance



The authors thank David Fraser (Biotech Communication SARL, Ploudalmézeau, France) for copy editing assistance. The authors also wish to thank Cosucra for kindly providing the inulin used in this project.

Authors’ contributions

HKC, FD, and VB designed the research program; HKC and FD conceived and designed the SHIME® and cell-based experiments, respectively; DOGA, MR, and LR performed the experiments and assays; DOGA, MR, and VB analyzed the data; SD contributed materials and analytical tools for the SHIME®; MR, DOGA, FD, and HKC wrote, evaluated, and revised the manuscript. All authors read and approved the final manuscript.

Funding information

This study is supported by the French Ministry of Research and Higher Education through MR’s postgraduate fellowship. They thank the Picardy Regional Council for providing funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11356_2018_2332_MOESM1_ESM.docx (47 kb)
ESM 1 (DOCX 47 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marina Réquilé
    • 1
    • 2
  • Dubàn O. Gonzàlez Alvarez
    • 1
    • 2
  • Stéphane Delanaud
    • 1
  • Larbi Rhazi
    • 2
  • Véronique Bach
    • 1
  • Flore Depeint
    • 2
  • Hafida Khorsi-Cauet
    • 1
  1. 1.Equipe PERITOX UMR-I01 INERIS, Centre Universitaire de Recherche en SantéUniversité Picardie Jules VerneAmiensFrance
  2. 2.UP 2018.C103 Transformations & Agro-RessourcesInstitut Polytechnique UniLaSalleBeauvaisFrance

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