The Preventive and Curative Effects of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 on Immobilization Stress-Induced Anxiety/Depression and Colitis in Mice

Nutrients. 2019 Apr 11;11(4):819. doi: 10.3390/nu11040819.


The gut dysbiosis by stressors such as immobilization deteriorates psychiatric disorders through microbiota-gut-brain axis activation. To understand whether probiotics could simultaneously alleviate anxiety/depression and colitis, we examined their effects on immobilization stress (IS)-induced anxiety/depression and colitis in mice. The probiotics Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 were isolated from healthy human feces. Mice with anxiety/depression and colitis were prepared by IS treatment. NK33 and NK98 potently suppressed NF-κB activation in lipopolysaccharide (LPS)-induced BV-2 cells. Treatment with NK33 and/or NK98, which were orally gavaged in mice before or after IS treatment, significantly suppressed the occurrence and development of anxiety/depression, infiltration of Iba1⁺ and LPS⁺/CD11b⁺ cells (activated microglia) into the hippocampus, and corticosterone, IL-6, and LPS levels in the blood. Furthermore, they induced hippocampal BDNF expression while NF-κB activation was suppressed. NK33 and/or NK98 treatments suppressed IS-induced colon shortening, myeloperoxidase activity, infiltration of CD11b⁺/CD11c⁺ cells, and IL-6 expression in the colon. Their treatments also suppressed the IS-induced fecal Proteobacteria population and excessive LPS production. They also induced BDNF expression in LPS-induced SH-SY5Y cells in vitro. In conclusion, NK33 and NK98 synergistically alleviated the occurrence and development of anxiety/depression and colitis through the regulation of gut immune responses and microbiota composition.

Keywords: Bifidobacterium adolescentis; Lactobacillus reuteri; anxiety; colitis; depression; immobilization stress.

MeSH terms

  • Animals
  • Anxiety / prevention & control
  • Anxiety / psychology
  • Anxiety / therapy*
  • Bifidobacterium adolescentis*
  • Cell Line
  • Colitis / psychology
  • Colitis / therapy*
  • Depression / prevention & control
  • Depression / psychology
  • Depression / therapy*
  • Dysbiosis / psychology
  • Humans
  • Lactobacillus reuteri*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • NF-kappa B / metabolism
  • Neuroblastoma
  • Probiotics / administration & dosage
  • Restraint, Physical
  • Stress, Psychological / complications*
  • Stress, Psychological / etiology
  • Tumor Cells, Cultured


  • Lipopolysaccharides
  • NF-kappa B