Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity

Susan Westfall, Francesca Caracci, Molly Estill, Tal Frolinger, Li Shen, Giulio M. Pasinetti

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate behavioral impairments linked to stress-induced immunological priming. The gut-brain-microbiota-axis is a promising therapeutic target for stress-induced behavioral impairments as it simultaneously modulates peripheral and brain immunological landscapes. In this study, a combination of probiotics and prebiotics, known as a synbiotic, promoted behavioral resilience to chronic and recurrent stress by normalizing gut microbiota populations and promoting regulatory T cell (Treg) expansion through modulation of ileal innate lymphoid cell (ILC)3 activity, an impact reflecting behavioral responses better than limbic brain region neuroinflammation. Supporting this conclusion, a multivariate machine learning model correlatively predicted a cross-tissue immunological signature of stress-induced behavioral impairment where the ileal Treg/T helper17 cell ratio associated to hippocampal chemotactic chemokine and prefrontal cortex IL-1β production in the context of stress-induced behavioral deficits. In conclusion, stress-induced behavioral impairments depend on the gut-brain-microbiota-axis and through ileal immune regulation, synbiotics attenuate the associated depressive- and anxiety-like behavior.

Original languageEnglish
Article number670500
JournalFrontiers in Immunology
StatePublished - 24 Jun 2021


  • innate lymphocyte cells
  • microbiota
  • nutraceutical
  • probiotic
  • psychiatry


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