Clostridium butyricum Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behavior in Mice via the Gut-Brain Axis

J Agric Food Chem. 2018 Aug 8;66(31):8415-8421. doi: 10.1021/acs.jafc.8b02462. Epub 2018 Jul 24.

Abstract

Abnormal gut microbiome has been associated with depression. The mechanism of probiotics against depression remains unclear. This study aimed to determine whether Clostridium butyricum (Cb) could attenuate chronic unpredictable mild stress-induced depressive-like behavior and its possible mechanisms. Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) and were treated with Cb. Depressive-like behavior was evaluated by a series of behavioral tests. The levels of cerebral 5-hydroxytryptamine (5-HT), brain derived neurotrophic factor (BDNF), glucagon-like peptide-1 (GLP-1) receptor and intestinal were measured. Cb treatment significantly improved CUMS-induced depressive-like behavior in mice. Meanwhile, Cb treatment exhibited prominent effects, increasing 5-HT and GLP-1 and upregulating BDNF expression. Furthermore, Cb-treated mice showed increased secretion of GLP-1 and upregulated GLP-1R expression. Taken together, our results demonstrate an antidepressive effect of Cb in CUMS mice partially attributed to stimulation of intestinal GLP-1 secretion and activation of cerebral GLP-1R.

Keywords: BDNF; depression; glucagon-like peptide-1; gut microbiota; probiotics.

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / physiology*
  • Brain Chemistry
  • Brain-Derived Neurotrophic Factor / analysis
  • Clostridium butyricum / physiology*
  • Depression / etiology
  • Depression / therapy*
  • Disease Models, Animal
  • Gastrointestinal Microbiome / physiology
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor / physiology
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / administration & dosage*
  • Serotonin / analysis
  • Stress, Psychological

Substances

  • Brain-Derived Neurotrophic Factor
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Serotonin
  • Glucagon-Like Peptide 1