Immobilization stress-induced Escherichia coli causes anxiety by inducing NF-κB activation through gut microbiota disturbance

• Published in: Scientific reports Vol. 8; no. 1; pp. 13897 - 14
• Main Authors: Jang, Hyo-Min, Lee, Kyung-Eon, Lee, Hae-Ji, Kim, Dong-Hyun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-09-2018; Nature Publishing Group
• Subjects: 13/21; 13/31; 13/51; 14/19; 631/477; 64/60; 692/617/375; 82/80; Animals; Anxiety; Anxiety - etiology; Anxiety - microbiology; Blood; Brain-derived neurotrophic factor; Cell activation; Colitis; Colitis - etiology; Colitis - microbiology; Colitis - therapy; Colon; Corticosterone; Digestive system; E coli; Escherichia coli; Escherichia coli - growth & development; Fecal Microbiota Transplantation; Fecal microflora; Feces; Gastrointestinal Microbiome; Gastrointestinal tract; Hippocampus; Humanities and Social Sciences; Immobilization; Immobilization - psychology; Inflammatory bowel disease; Intestinal microflora; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microbiota; Microglia; Monocytes; multidisciplinary; NF-kappa B - metabolism; NF-κB protein; Oral administration; Probiotics; Probiotics - administration & dosage; Proteobacteria; Science; Science (multidisciplinary); Stress, Physiological; Tumor necrosis factor-α; Brain-derived Neurotrophic Factor (BDNF); Commensal Lactobacilli; BDNF Expression; Johnsonii; Anxiety-like Behavior
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-31764-0

The present study aimed to understand the crosstalk between anxiety and gut microbiota. Exposure of mice to immobilization stress (IS) led to anxiety-like behaviors, increased corticosterone and tumor necrosis factor-α levels in the blood, increased nuclear factor (NF)-κB activation and microglia/monocyte populations in the hippocampus, and suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Furthermore, IS exposure increased NF-κB activation and monocyte population in the colon and increased Proteobacteria and
Escherichia coli
populations in the gut microbiota and fecal and blood lipopolysaccharide (LPS) levels while decreasing the
lactobacilli
population. Oral administration of the fecal microbiota of mice treated with IS (FIS) or
E
.
coli
led to the increased NF-κB activation and monocyte population in the colon. These treatments increased blood corticosterone and LPS levels and anxiety-like behaviors, decreased BDNF expression, and induced NF-κB activation and microglia/monocyte populations in the hippocampus. Intraperitoneal injection of LPS purified from
E
.
coli
also led to anxiety and colitis in mice. Oral administration of commensal
lactobacilli
, particularly
Lactobacillus johnsonii
, attenuated IS- or
E
.
coli
-induced colitis and anxiety-like behaviors and biomarkers. These findings suggest that exposure to stressors can increase Proteobacteria populations and fecal LPS levels and cause gastrointestinal inflammation, resulting in the deterioration of anxiety through NF-κB activation. However, the amelioration of gastrointestinal inflammation by treatment with probiotics including
L
.
johnsonii
can alleviate anxiety.