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.
摘要：
肠道微生物群通过神经与大脑双向沟通，免疫，和肠道的内分泌系统。在我们的初步研究中,轻度认知障碍（Fmci）志愿者的粪便微生物群表现出较高丰度的大肠杆菌（NK2001），Veillonellainfantium(NK2002),和屎肠球菌(NK2003)人群与健康志愿者的人群相比。因此,我们检查了FMCI的影响，NK2001（革兰氏阴性），NK2002(革兰氏阴性)，和NK2003(革兰氏阳性)对认知障碍样行为，神经炎症，和有或没有抗生素的小鼠结肠炎。Fmci移植增加了认知障碍样行为，海马肿瘤坏死因子(TNF)-α表达,Toll样受体(TLR)4+Iba1+的大小，TLR2+Iba1+,和NF-κB+Iba1+细胞群体独立于抗生素治疗。NK2001，NK2002或NK2003的口服管饲法诱导TNF-α在Caco-2细胞中的表达，小鼠认知障碍样行为和海马TNF-α表达和Iba1阳性细胞群显著增加，脑源性神经营养因子(BDNF)表达降低。腹腔迷走神经切断术显着降低了NK2001-或NK2002诱导的认知障碍样行为和海马Iba1细胞群和TNF-α表达，并增加了NK2001-或NK2002抑制的海马BDNF表达。然而,NK2003诱导的认知功能障碍样行为和海马Iba1+细胞群和TNF-α表达均部分,但并不重要，腹腔迷走神经切断术减毒。此外，腹腔迷走神经切断术不影响NK2001-，NK2002-,或NK2003诱导的血液和粪便中的脂多糖（LPS）水平以及结肠中TNF-α表达和NF-κB阳性细胞群。总之,产生LPS的NK2001和NK2002和不产生LPS的NK2003可能通过LPS和肽聚糖等副产物通过肠-血/迷走神经-脑和肠-血-脑途径易位进入大脑，从而诱导NF-κB介导的神经炎症。分别,导致认知障碍。
