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조회798

경희대학교 약학대학

Brain Behav. Immun., Feb 28 2024, 118 S0889-1591(24)00277-0 | https://doi.org/10.1016/j.bbi.2024.02.031 Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice

Xiaoyang Ma ^a, Jeon-Kyung Kim ^a,b, Yoon-Jung Shin ^a, Hee-Seo Park ^a, Dong-Yun Lee ^a, Sung-Vin Yim ^c, Dong-Hyun Kim ^a

^aNeurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, Korea

^bSchool of Pharmacy, Jeonbuk National University, Jeonju-si, Korea

^cDepartment of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Korea

Corresponding author: Dong-Hyun Kim

Abstract

Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4 ⁺Iba1 ⁺, TLR2 ⁺Iba1 ⁺, and NF-κB ⁺Iba1 ⁺ cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1 ⁺ cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1 ⁺ cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-03-05)
연구진국내 연구진
분야 의약학 > 약학

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