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Peer-reviewedCC BY 4.0PLOS One

Feeding a low-protein diet exacerbates the susceptibility to Citrobacter rodentium and dextran sulfate sodium-induced intestinal injury in mice

  • Mehakpreet K. Thind1
  • Mary Flanagan2
  • Sanne de Wit3
  • Aida Glembocki4
  • Jiali Pan5
  • Celine Cuinat6
  • Sharon Leung7
  • Shamsun Nahar Shaima8
  • Hamza Sghayare9
  • Kinza Usmani10
  • Mishaal Munawar
  • Peter Kim
4 more authors
  • Elena M. Comelli
  • Amber Farooqui
  • Celine Bourdon
  • Robert H. J. Bandsma
10 affiliations
  1. 1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  2. 2Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
  3. 3Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
  4. 4Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands
  5. 5Department of Pathology and Laboratory Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
  6. 6Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada
  7. 7Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
  8. 8Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada
  9. 9Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  10. 10Centre for Child Nutrition and Health, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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Abstract

Globally, almost half of all early childhood deaths are linked to severe undernutrition, herein referred to as severe malnutrition. Mortality in severely malnourished children is often attributed to common infectious diseases, including enteric infections. It has been proposed that impaired intestinal barrier function contributes to mortality, but direct evidence is limited and thus there exists a need to develop improved preclinical models to test these and other mechanistic hypotheses. In this study, we aimed to describe differences in response to enteric inflammation and infection in the colon of malnourished mice compared to well-nourished littermates. C57Bl/6 male weanlings were fed isocaloric diets, either a low 1% protein diet (LPD) or a control 18% protein diet (CPD) for 2-weeks either in combination with oral administration of dextran sodium sulfate (DSS), or Citrobacter rodentium (C. rodentium). LPD-fed mice were more susceptible to DSS or C. rodentium as evidenced by increased clinical severity scores, and reaching their humane endpoints. LPD-fed mice also showed more signs of colonic dysfunction with reduced levels of tight junction proteins, higher colonic pathogen load, and increased systemic inflammation and bacterial spread. Taken together, these observations show that malnourished animals have increased susceptibility to intestinal dysfunction caused by either chemical exposure or infection. These novel preclinical models can be used to further elucidate the processes involved in enteric dysfunction in malnutrition and to test therapies to improve intestinal repair and outcomes.

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Cite

BibTeXRIS
BibTeX
@article{thind2026feeding,
  title = {{Feeding a low-protein diet exacerbates the susceptibility to Citrobacter rodentium and dextran sulfate sodium-induced intestinal injury in mice}},
  author = {Mehakpreet K. Thind and Mary Flanagan and Sanne de Wit and Aida Glembocki and Jiali Pan and Celine Cuinat and Sharon Leung and Shamsun Nahar Shaima and Hamza Sghayare and Kinza Usmani and Mishaal Munawar and Peter Kim and Elena M. Comelli and Amber Farooqui and Celine Bourdon and Robert H. J. Bandsma},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0335322},
  url = {https://doi.org/10.1371/journal.pone.0335322},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Feeding a low-protein diet exacerbates the susceptibility to Citrobacter rodentium and dextran sulfate sodium-induced intestinal injury in mice
AU  - Mehakpreet K. Thind
AU  - Mary Flanagan
AU  - Sanne de Wit
AU  - Aida Glembocki
AU  - Jiali Pan
AU  - Celine Cuinat
AU  - Sharon Leung
AU  - Shamsun Nahar Shaima
AU  - Hamza Sghayare
AU  - Kinza Usmani
AU  - Mishaal Munawar
AU  - Peter Kim
AU  - Elena M. Comelli
AU  - Amber Farooqui
AU  - Celine Bourdon
AU  - Robert H. J. Bandsma
PY  - 2026
DA  - 2026/10/07
JO  - PLOS One
DO  - 10.1371/journal.pone.0335322
UR  - https://doi.org/10.1371/journal.pone.0335322
AB  - Globally, almost half of all early childhood deaths are linked to severe undernutrition, herein referred to as severe malnutrition. Mortality in severely malnourished children is often attributed to common infectious diseases, including enteric infections. It has been proposed that impaired intestinal barrier function contributes to mortality, but direct evidence is limited and thus there exists a need to develop improved preclinical models to test these and other mechanistic hypotheses. In this study, we aimed to describe differences in response to enteric inflammation and infection in the colon of malnourished mice compared to well-nourished littermates. C57Bl/6 male weanlings were fed isocaloric diets, either a low 1% protein diet (LPD) or a control 18% protein diet (CPD) for 2-weeks either in combination with oral administration of dextran sodium sulfate (DSS), or Citrobacter rodentium (C. rodentium). LPD-fed mice were more susceptible to DSS or C. rodentium as evidenced by increased clinical severity scores, and reaching their humane endpoints. LPD-fed mice also showed more signs of colonic dysfunction with reduced levels of tight junction proteins, higher colonic pathogen load, and increased systemic inflammation and bacterial spread. Taken together, these observations show that malnourished animals have increased susceptibility to intestinal dysfunction caused by either chemical exposure or infection. These novel preclinical models can be used to further elucidate the processes involved in enteric dysfunction in malnutrition and to test therapies to improve intestinal repair and outcomes.
SN  - 1932-6203
ER  -