Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress

Neuroscience. 2015 Dec 3;310:561-77. doi: 10.1016/j.neuroscience.2015.09.033. Epub 2015 Sep 25.


Increasing numbers of studies have suggested that the gut microbiota is involved in the pathophysiology of stress-related disorders. Chronic stress can cause behavioral, cognitive, biochemical, and gut microbiota aberrations. Gut bacteria can communicate with the host through the microbiota-gut-brain axis (which mainly includes the immune, neuroendocrine, and neural pathways) to influence brain and behavior. It is hypothesized that administration of probiotics can improve chronic-stress-induced depression. In order to examine this hypothesis, the chronic restraint stress depression model was established in this study. Adult specific pathogen free (SPF) Sprague-Dawley rats were subjected to 21 days of restraint stress followed by behavioral testing (including the sucrose preference test (SPT), elevated-plus maze test, open-field test (OFT), object recognition test (ORT), and object placement test (OPT)) and biochemical analysis. Supplemental Lactobacillus helveticus NS8 was provided every day during stress until the end of experiment, and selective serotonin reuptake inhibitor (SSRI) citalopram (CIT) served as a positive control. Results showed that L. helveticus NS8 improved chronic restraint stress-induced behavioral (anxiety and depression) and cognitive dysfunction, showing an effect similar to and better than that of CIT. L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels, and more hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression than in chronic stress rats. Taken together, these results indicate an anti-depressant effect of L. helveticus NS8 in rats subjected to chronic restraint stress depression and that this effect could be due to the microbiota-gut-brain axis. They also suggest the therapeutic potential of L. helveticus NS8 in stress-related and possibly other kinds of depression.

Keywords: BDNF; Lactobacillus helveticus; chronic restraint stress; depression; microbiota–gut–brain axis; serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Anxiety / etiology
  • Anxiety / metabolism
  • Anxiety / prevention & control*
  • Behavior, Animal* / drug effects
  • Body Weight / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Citalopram / pharmacology
  • Corticosterone / blood
  • Depression / etiology
  • Depression / metabolism
  • Depression / prevention & control*
  • Dopamine / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Lactobacillus helveticus*
  • Male
  • Norepinephrine / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Probiotics / administration & dosage*
  • Probiotics / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / pharmacology
  • Stress, Psychological / complications*
  • Tumor Necrosis Factor-alpha / blood


  • Brain-Derived Neurotrophic Factor
  • Serotonin Uptake Inhibitors
  • Tumor Necrosis Factor-alpha
  • Citalopram
  • Interleukin-10
  • Serotonin
  • Interferon-gamma
  • Adrenocorticotropic Hormone
  • Dopamine
  • Corticosterone
  • Norepinephrine