The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy.
The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy.
复制标题
肠道微生物和代谢物对脓毒症相关脑病血脑屏障完整性和脑功能的调节作用。
作者：
Li Z;Zhang F;Sun M;Liu J;Zhao L;Liu S;Li S;Wang B
Intestinal microbiota homeostasis and the gut-brain axis are key players associated with host health and alterations in metabolic, inflammatory, and neurodegenerative disorders. Sepsis-associated encephalopathy (SAE), which is closely associated with bacterial translocation, is a common secondary organ dysfunction and an urgent, unsolved problem affecting patient quality of life. Our study examined the neuroprotective effects of the gut microbiome and short-chain fatty acid (SCFA) metabolites on SAE. Male C57BL/6 mice were administered SCFAs in drinking water, then subjected to cecal ligation and puncture (CLP) surgery to induce SAE. 16S rRNA sequencing was used to investigate gut microbiome changes. The open field test (OFT) and Y-maze were performed to evaluate brain function. The permeability of the blood–brain barrier (BBB) was assessed by Evans blue (EB) staining. Hematoxylin and eosin (HE) staining was used to examine intestinal tissue morphology. The expression levels of tight junction (TJ) proteins and inflammatory cytokines was assessed by western blots and immunohistochemistry. In vitro, bEND.3 cells were incubated with SCFAs and then with lipopolysaccharide (LPS). Immunofluorescence was used to examine the expression of TJ proteins. The composition of the gut microbiota was altered in SAE mice; this change may be related to SCFA metabolism. SCFA treatment significantly alleviated behavioral dysfunction and neuroinflammation in SAE mice. SCFAs upregulated occludin and ZO-1 expression in the intestine and brain in SAE mice and LPS-treated cerebromicrovascular cells. These findings suggested that disturbances in the gut microbiota and SCFA metabolites play key roles in SAE. SCFA supplementation could exert neuroprotective effects against SAE by preserving BBB integrity.
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影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
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：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
5
作者：
Gallier S;Van den Abbeele P;Prosser C
通讯作者：
Prosser C
DOI：
10.1038/nrgastro.2010.117
发表时间：
2010-09
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Gareau MG;Sherman PM;Walker WA
通讯作者：
Walker WA