The Gut-Ex-Vivo System (GEVS) Is a Dynamic and Versatile Tool for the Study of DNBS-Induced IBD in BALB/C and C57BL/6 Mice, Highlighting the Protective Role of Probiotics

Romina Monzani, Mara Gagliardi, Nausicaa Clemente, Valentina Saverio, Elżbieta Pańczyszyn, Claudio Santoro, Nissan Yissachar, Annalisa Visciglia, Marco Pane, Angela Amoruso, Marco Corazzari

Research output: Contribution to journalArticlepeer-review

Abstract

Background: IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against the intestine, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for disease onset and progression are still elusive, thus requiring intense research effort. In this context, the development of models replicating the etiopathology of IBD and allowing the testing of new potential therapies is critical. Methods: Colon from C57BL/6 or BALB/c mice was cultivated in a Gut-Ex-Vivo System (GEVS), exposed for 5 h to DNBS 1.5 or 2.5 mg/mL, in presence or absence of two probiotic formulations (P1 = Bifidobacterium breve BR03 (DSM16604) and B632 (DSM24706); P2 = Lacticaseibacillus rhamnosus LR04 (DSM16605), Lactiplantibacillus plantarum LP14 (DSM33401) and Lacticaseibacillus paracasei LPC09), and the main hallmarks of IBD were evaluated. Results: Gene expression analysis revealed the following DNBS-induced effects: (i) compromised tight junction organization, responsible for tissue permeability dysregulation; (ii) induction of ER stress, and (iii) tissue inflammation in colon of C57BL/6 mice. Moreover, the concomitant DNBS-induced apoptosis and ferroptosis pathways were evident in colon from both BALB/c and C57BL/6 mice. Finally, the co-administration of probiotics completely prevented the detrimental effects of DNBS. Conclusions: Overall, we have provided results demonstrating that GEVS is a consistent, reliable, and cost-effective system for modeling DNBS-induced IBD, useful for studying the onset and progression of human disease at the molecular level, while also reducing animal suffering. Moreover, we have confirmed the beneficial effect of probiotics administration in promoting the remission of IBD.

Original languageEnglish
Article number1574
JournalBiology
Volume11
Issue number11
DOIs
StatePublished - 27 Oct 2022

Bibliographical note

Funding Information:
This work was supported by the Italian Ministry of Education, University and Research (MIUR) program “Departments of Excellence 2018–2022”, FOHN Project—Department of Health Sciences, Università del Piemonte Orientale. The support of FAR 2019 (Progetti di Ateneo), the EU grant “PREMUROSA” (ID #860462), “ExcellMater” (ID #952033) H2020 projects, and AGING Project—Department of Excellence—DIMET are also acknowledged. E.P. was supported by H2020 EU grant (PREMUROSA).

Publisher Copyright:
© 2022 by the authors.

Keywords

  • DNBS
  • GEVS
  • Gut-Ex-Vivo System
  • IBD
  • UPR
  • apoptosis
  • ex vivo organ
  • ferroptosis
  • probiotics

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