biostudies-literatureKang DJBLRD VAVA Merit ReviewNIDDK NIH HHSNIAAA NIH HHSNIDDKMcGuire Research InstituteNational Gnotobiotic Rodent Resource Center (NGRRC)NIH HHSCSRD VA1232-48https://www.ebi.ac.uk/biostudies/studies/S-EPMC5033692biostudies-literatureUnknown64(4)<h4>Unlabelled</h4>The mechanisms behind the development of hepatic encephalopathy (HE) are unclear, although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. The aim of this work was to define the individual contribution of hyperammonemia and systemic inflammation on neuroinflammation in cirrhosis using germ-free (GF) and conventional mice. GF and conventional C57BL/6 mice were made cirrhotic using CCl4 gavage. These were compared to their noncirrhotic counterparts. Intestinal microbiota, systemic and neuroinflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity, and cecal glutamine content were compared between groups. GF cirrhotic mice developed similar cirrhotic changes to conventional mice after 4 extra Hepatology (Baltimore, Md.)Gut microbiota drive the development of neuroinflammatory response in cirrhosis in mice.PMC5033692R01 AA0202035-P30-DK034987I01 CX001076P30 DK034987I01 BX0013285-P40-OD010995R01DK089713P40 OD010995CX10076R01 DK087913Kang DJGhosh SAYang JBajaj JSLiu RBetrapally NSJiao CLippman HRHylemon PBSikaroodi MSartor RBSanyal AJBrown RRHerzog JGillevet PMWang XCarl DZhou HHeuman DMfalseGut microbiota drive the development of neuroinflammatory response in cirrhosis in mice.<h4>Unlabelled</h4>The mechanisms behind the development of hepatic encephalopathy (HE) are unclear, although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. The aim of this work was to define the individual contribution of hyperammonemia and systemic inflammation on neuroinflammation in cirrhosis using germ-free (GF) and conventional mice. GF and conventional C57BL/6 mice were made cirrhotic using CCl4 gavage. These were compared to their noncirrhotic counterparts. Intestinal microbiota, systemic and neuroinflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity, and cecal glutamine content were compared between groups. GF cirrhotic mice developed similar cirrhotic changes to conventional mice after 4 extra 2016-01-01T00:00:00Z2016 Oct2025-04-19T03:03:10.552Z2019-03-27T02:24:54ZS-EPMC50336922733973210.1002/hep.28696