Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models

Neurogastroenterol Motil. 2016 Jul;28(7):1027-36. doi: 10.1111/nmo.12804. Epub 2016 Feb 20.


Background: This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions.

Methods: Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS-fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats.

Key results: Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner.

Conclusions & inferences: These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.

Keywords: cortisol; gut-brain axis; probiotics; stress; vagus.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cultured Milk Products
  • Double-Blind Method
  • Female
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism*
  • Humans
  • Hydrocortisone / metabolism
  • Lacticaseibacillus casei*
  • Male
  • Models, Animal*
  • Probiotics / pharmacology
  • Probiotics / therapeutic use*
  • Rats
  • Rats, Inbred F344
  • Saliva / drug effects
  • Saliva / metabolism
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology
  • Young Adult


  • Hydrocortisone