AD等神经精神障碍可能导致肠道炎症和菌群失调。抑制肠道炎症的益生菌可以缓解神经精神障碍。为了研究能否缓解认知功能障碍的抗炎益生菌Lactobacillus mucosae NK41和Bifidobacterium longum NK46（可抑制脂多糖（LPS）刺激的巨噬细胞中的肿瘤坏死因子（TNF）-α表达），我们首先检查了它们对5xFAD转基因小鼠的认知功能，肠道炎症和肠道微生物组成的影响。NK41或NK46的口服给药可减轻认知功能障碍样行为、海马β（Aβ）、TNF-α和白细胞介素（IL）-1β表达、海马核因子-κB（NF-κB）+/微胶质细胞标记（Iba1）+细胞数量和Aβ沉积，同时增加海马脑源性神经营养因子（BDNF）和IL-10的表达以及BDNF+/神经核细胞核标记（NeuN）+细胞数量。而且，它们还减少了结肠中TNF-α和IL-1β的表达以及NF-κB+/CD11c+细胞数量。还降低了粪便和血液中的LPS水平以及肠道变形菌科和Verrucomicrobia门（包括Akkkermansiaceae）的数量（与海马TNF-α和粪便LPS水平呈正相关，与海马BDNF水平呈负相关）。然而，它们增加了烟雾杆菌科，它与BDNF表达水平和TNF-α与IL-10表达比例呈正相关。NK41和NK46（比例为4:1，称为NKc）的联合组合（在LPS刺激的巨噬细胞中有效抑制TNF-α表达），在5xFAD转基因或老年小鼠中协同缓解了认知功能障碍样行为。NKc增加了5xFAD转基因或老年小鼠海马BDNF+/NeuN+细胞数量和BDNF的表达，减少了海马TNF-α和IL-1β的表达。NKc还减少了结肠中TNF-α和IL-1β的表达以及血液和粪便中的LPS水平。这些发现表明，肠道细菌及其产物LPS可能与认知功能障碍和神经炎症的发生密切相关，而NK41和NK46的联合组合可以通过诱导抑制NF-κB的BDNF表达和抑制产生LPS的肠道细菌来协同缓解认知功能障碍和神经炎症。

Neuropsychiatric disorders including Alzheimer's disease (AD) may cause gut inflammation and dysbiosis. Gut inflammation-suppressing probiotics alleviate neuropsychiatric disorders. Herein, to understand whether anti-inflammatory probiotics Lactobacillus mucosae NK41 and Bifidobacterium longum NK46, which suppressed tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated macrophages, could alleviate cognitive impairment, we first examined their effects on cognitive function, gut inflammation, and gut microbiota composition in 5xFAD-transgenic mice. Oral administration of NK41 or NK46 decreased cognitive impairment-like behaviors, hippocampal amyloid-β (Aβ), TNF-α and interleukin (IL)-1β expression, hippocampal NF-κB+Iba1+ cell population, and Aβ accumulation, while hippocampal brain-derived neurotropic factor (BDNF) and IL-10 expression and BDNF+NeuN+ cell population increased. They also decreased TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. They also reduced fecal and blood LPS levels and gut Proteobacteria and Verrucomicrobia populations (including Akkkermansiaceae), which are positively associated with hippocampal TNF-α and fecal LPS levels and negatively correlated with hippocampal BDNF level. However, they increased Odoribactericeae, which positively correlated with BDNF expression level and TNF-α to IL-10 expression ratio. The combination of NK41 and NK46 (4:1, NKc), which potently inhibited TNF-α expression in LPS-stimulated macrophages, additively alleviated cognitive impairment-like behaviors in 5xFAD-transgenic or aged mice. NKc increased hippocampal BDNF+NeuN+ cell population and BDNF expression in 5xFAD-transgenic or aged mice, while hippocampal TNF-α and IL-1β expression decreased. NKc also decreased TNF-α and IL-1β expression in the colon and LPS levels in the blood and feces. These findings suggest that gut bacteria and its product LPS may be closely connected with occurrence of cognitive impairment and neuroinflammation and the combination of NK41 and NK46 can additively alleviate cognitive impairment and neuroinflammation by inducing NF-κB-suppressed BDNF expression and suppressing LPS-producing gut bacteria.