The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice

• Published in: Journal of neuroinflammation Vol. 21; no. 1; pp. 224 - 16
• Main Authors: Ma, Xiaoyang, Park, Hee-Seo, Shin, Yoon-Jung, Kim, Jeon-Kyung, Hong, Jung Kyung, Han, Seung-Won, Yoon, In-Young, Kim, Dong-Hyun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.09.2024; BMC
• Subjects: Animals; Depression; Depression - etiology; Depression - metabolism; Depression, Mental; Enterobacter; Enterobacteriaceae; Enterococcus faecium; Escherichia fergusonii; Extracellular Vesicles - metabolism; Gut dysbiosis; Health aspects; Humans; Inflammation; Male; Medical research; Medicine, Experimental; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases - metabolism; Particles; Physiological aspects; Psychological aspects; Vagotomy; Vagus nerve; Vagus Nerve - metabolism; South Korea; Enterococcus faecium; Depression; Gut dysbiosis; Escherichia fergusonii; Vagus nerve
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-024-03211-7

Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy. Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB Iba1 and lipopolysaccharide (LPS) Iba1 cell populations, while decreasing serotonin, 5-HT receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone. esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.