The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1⁺), monocytes (CD11b⁺/CD45⁺), and dendritic cells (CD11b⁺/CD11c⁺) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3⁺/NeuN⁺) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1β and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.

中文翻译：

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抗菌药物引起的肠道菌群紊乱、神经炎症和小鼠焦虑之间相互作用的证据。

本研究的目的是确定抗菌依赖性肠道菌群紊乱与焦虑之间是否存在机制联系。首先，小鼠暴露于氨苄青霉素会引起焦虑和结肠炎，并增加肠道菌群中变形菌的数量，尤其是产酸克雷伯氏菌、粪便和血液脂多糖水平，同时减少包括罗伊氏乳杆菌在内的乳酸菌数量。接下来，用氨苄青霉素处理的小鼠 (FAP) 的粪便微生物群、催产克氏杆菌或从催产克氏杆菌 (KL) 分离的脂多糖进行处理，可诱导小鼠焦虑和结肠炎，并增加血液皮质酮、IL-6 和脂多糖水平。此外，这些治疗还增加了小胶质细胞 (Iba1 ⁺ )、单核细胞 (CD11b ⁺/CD45 ⁺ ) 和树突状细胞 (CD11b ⁺ /CD11c ⁺ ) 到海马体，以及大脑中的凋亡神经元细胞群 (caspase-3 ⁺ /NeuN ⁺ )。此外，氨苄西林、K. oxytoca 和 KL 在结肠和大脑中诱导 NF-κB 激活和 IL-1β 和 TNF-α 表达，并增加肠膜通透性。最后，口服 L. reuteri 可减轻氨苄西林引起的焦虑和结肠炎。这些结果表明，氨苄青霉素暴露可通过神经炎症引起焦虑，神经炎症可由单核细胞/巨噬细胞激活的胃肠道炎症和包括催产克氏杆菌在内的变形杆菌数量增加引起，而用乳酸杆菌治疗可抑制焦虑。