Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice

Carli J. Smith, Jacob R. Emge, Katrina Berzins, Lydia Lung, Rebecca Khamishon, Paarth Shah, Colin Reardon, Kim E. Barrett, Melanie Gareau, David M. Rodrigues, Andrew J. Sousa, Philip M. Sherman, Mélanie G. Gareau, Colin Reardon

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1−/− mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis.

Original languageEnglish (US)
Pages (from-to)G793-G802
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume307
Issue number8
DOIs
StatePublished - Oct 15 2014

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Probiotics
Dysbiosis
Psychological Stress
Brain
Anxiety
Microbiota
Insurance Benefits
Immune System
B-Lymphocytes
Lymphocytes
T-Lymphocytes
Health
Gastrointestinal Microbiome
Therapeutics

Keywords

  • Anxiety
  • Behavior
  • Memory
  • Microbiota
  • Probiotics
  • Stress

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology
  • Medicine(all)

Cite this

Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice. / Smith, Carli J.; Emge, Jacob R.; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Reardon, Colin; Barrett, Kim E.; Gareau, Melanie; Rodrigues, David M.; Sousa, Andrew J.; Sherman, Philip M.; Gareau, Mélanie G.; Reardon, Colin.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 307, No. 8, 15.10.2014, p. G793-G802.

Research output: Contribution to journalArticle

Smith, CJ, Emge, JR, Berzins, K, Lung, L, Khamishon, R, Shah, P, Reardon, C, Barrett, KE, Gareau, M, Rodrigues, DM, Sousa, AJ, Sherman, PM, Gareau, MG & Reardon, C 2014, 'Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 307, no. 8, pp. G793-G802. https://doi.org/10.1152/ajpgi.00238.2014
Smith, Carli J. ; Emge, Jacob R. ; Berzins, Katrina ; Lung, Lydia ; Khamishon, Rebecca ; Shah, Paarth ; Reardon, Colin ; Barrett, Kim E. ; Gareau, Melanie ; Rodrigues, David M. ; Sousa, Andrew J. ; Sherman, Philip M. ; Gareau, Mélanie G. ; Reardon, Colin. / Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2014 ; Vol. 307, No. 8. pp. G793-G802.
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