IL-6 expression-suppressing Lactobacillus reuteri strains alleviate gut microbiota-induced anxiety and depression in mice

Lett Appl Microbiol. 2024 Jan 2;77(1):ovad144. doi: 10.1093/lambio/ovad144.

Abstract

Fecal microbiota transplantation from patients with depression/inflammatory bowel disease (PDI) causes depression with gut inflammation in mice. Here, we investigated the effects of six Lactobacillus reuteri strains on brain-derived neurotropic factor (BDNF), serotonin, and interleukin (IL)-6 expression in neuronal or macrophage cells and PDI fecal microbiota-cultured microbiota (PcM)-induced depression in mice. Of these strains, L6 most potently increased BDNF and serotonin levels in corticosterone-stimulated SH-SY5Y and PC12 cells, followed by L3. L6 most potently decreased IL-6 expression in lipopolysaccharide (LPS)-stimulated macrophages. When L1 (weakest in vitro), L3, and L6 were orally administered in mice with PcM-induced depression, L6 most potently suppressed depression-like behaviors and hippocampal TNF-α and IL-6 expression and increased hippocampal serotonin, BDNF, 5HT7, GABAARα1, and GABABR1b expression, followed by L3 and L1. L6 also suppressed TNF-α and IL-6 expression in the colon. BDNF or serotonin levels in corticosterone-stimulated neuronal cells were negatively correlated with depression-related biomarkers in PcM-transplanted mice, while IL-6 levels in LPS-stimulated macrophage were positively correlated. These findings suggest that IL-6 expression-suppressing and BDNF/serotonin expression-inducing LBPs in vitro, particularly L6, may alleviate gut microbiota-involved depression with colitis in vivo.

Keywords: Lactobacillus reuteri; IL-6; depression; gut microbiota; inflammation; serotonin.

MeSH terms

  • Animals
  • Anxiety / etiology
  • Anxiety / therapy
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Corticosterone / pharmacology
  • Depression / therapy
  • Gastrointestinal Microbiome*
  • Humans
  • Interleukin-6 / genetics
  • Limosilactobacillus reuteri*
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Neuroblastoma*
  • Rats
  • Serotonin / pharmacology
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Lipopolysaccharides
  • Corticosterone
  • Serotonin
  • Brain-Derived Neurotrophic Factor