Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice.
Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice.
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DOI：
10.1186/s12974-023-02825-7
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发表时间：
2023-07-15
影响因子：
9.3
通讯作者：
Gao, Hongchang
中科院分区：
文献类型：
--
作者：
Zheng, Hong;Zhao, Qihui;Chen, Jianuo;Lu, Jiahui;Li, Yuping;Gao, Hongchang
急性呼吸窘迫综合征(ARDS)是一种呼吸衰竭综合征，可引起多种并发症，影响患者的生活质量。行为和认知障碍在ARDS患者中引起了越来越多的关注，但其潜在的机制仍不清楚。在这里，我们将社区获得性肺炎(CAP)引起的ARDS患者的粪便微生物群转移到接受抗生素治疗的雄性小鼠身上，以探索微生物群-肠道-脑的机制。通过旷场实验、Morris水迷宫和Y迷宫实验评价小鼠的行为功能。通过16S rRNA测序分析肠道微生物区系的结构和组成。免疫荧光染色检测皮质和海马区的小胶质细胞、星形胶质细胞和神经元。我们发现ARDS/CAP患者肠道菌群的主要特征是革兰氏阴性菌数量高于正常对照组。来自ARDS/CAP患者的肠道微生物区系促进了小鼠的神经炎症和行为功能障碍。接受ARDS/CAP患者粪便移植的小鼠出现了系统内毒素(LPS)增加、全身炎症和结肠屏障通透性增加。这可能会对血屏障通透性造成不利影响，并促进小胶质细胞的激活、星形胶质细胞的增殖和神经元的丢失。我们的研究提出了微生物区系-肠道-脑串扰在ARDS/CAP相关行为损害中的作用，并建议肠道微生物区系在临床实践中作为保护ARDS患者脑健康的潜在靶点。网上版载有补充材料，可在10.1186/s12974-023-02825-7查阅。
Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome that can cause many complications, impacting patients’ quality of life. Behavioral and cognitive disorders have attracted increasing attention in patients with ARDS, but its potential mechanisms are still elusive. Herein we transferred the faecal microbiota from patients with ARDS caused by community-acquired pneumonia (CAP) to antibiotics-treated recipient male mice to explore the microbiota-gut-brain mechanisms. Behavioral functions of mice were evaluated by the open field test, Morris water maze and Y-maze test. The structure and composition of the gut microbiota were analyzed by using 16S rRNA sequencing analysis. Microglia, astrocyte and neuron in the cortex and hippocampus were examined via immunofluorescent staining. We found that the major characteristic of the intestinal flora in ARDS/CAP patients was higher abundances of Gram-negative bacteria than normal controls. The gut microbiota derived from ARDS/CAP patients promoted neuroinflammation and behavioral dysfunctions in mice. Mice who underwent fecal transplant from ARDS/CAP patients had increased systemic lipopolysaccharide (LPS), systemic inflammation, and increased colonic barrier permeability. This may adversely impact blood barrier permeability and facilitate microglia activation, astrocyte proliferation, and loss of neurons. Our study proposes the role of the microbiota-gut-brain crosstalk on ARDS/CAP-associated behavioral impairments and suggests the gut microbiota as a potential target for the protection of brain health in ARDS patients in clinical practice. The online version contains supplementary material available at 10.1186/s12974-023-02825-7.
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影响因子：
12.6
作者：
Kim HS;Kim S;Shin SJ;Park YH;Nam Y;Kim CW;Lee KW;Kim SM;Jung ID;Yang HD;Park YM;Moon M
通讯作者：
Moon M
影响因子：
15.5
作者：
D'Amato A;Di Cesare Mannelli L;Lucarini E;Man AL;Le Gall G;Branca JJV;Ghelardini C;Amedei A;Bertelli E;Regoli M;Pacini A;Luciani G;Gallina P;Altera A;Narbad A;Gulisano M;Hoyles L;Vauzour D;Nicoletti C
通讯作者：
Nicoletti C
影响因子：
24.5
作者：
Camilleri, Michael
通讯作者：
Camilleri, Michael
影响因子：
81.5
作者：
Matthay, Michael A.;Zemans, Rachel L.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.
影响因子：
48
作者：
Edgar, Robert C.
通讯作者：
Edgar, Robert C.