Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis-Induced Liver Injury by Granisetron Generation in Mice.
Animals
Coinfection
/ complications
Cytochrome P-450 CYP1A1
/ metabolism
Cytokines
/ metabolism
Gastrointestinal Microbiome
Granisetron
/ metabolism
Humans
Liver Diseases
/ microbiology
Male
Mice
Mice, Inbred C57BL
NF-kappa B
/ metabolism
RAW 264.7 Cells
Receptors, Serotonin, 5-HT3
/ genetics
Sepsis
/ microbiology
Toll-Like Receptor 4
/ metabolism
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
07
08
2018
accepted:
13
11
2018
pubmed:
7
12
2018
medline:
30
5
2020
entrez:
4
12
2018
Statut:
ppublish
Résumé
Sepsis-induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res; survived to 7 days after CLP) and sepsis-sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more-severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT
Substances chimiques
Cytokines
0
NF-kappa B
0
Receptors, Serotonin, 5-HT3
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Cyp1a1 protein, mouse
EC 1.14.14.1
Cytochrome P-450 CYP1A1
EC 1.14.14.1
Granisetron
WZG3J2MCOL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1751-1767Subventions
Organisme : Natural Science Funds for Distinguished Young Scholar of Guangdong province
ID : 2016A030306043
Pays : International
Organisme : the funding from State Key Laboratory of Organ Failure Research
ID : 201804
Pays : International
Organisme : NSFC-Guangdong Joint Foundation of China
ID : U1601225
Pays : International
Organisme : Key Scientific and Technological Program of Guangzhou City
ID : 201607020016
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81372030
Pays : International
Organisme : the award of Young Pearl Scholars of Guangdong province
ID : N/A
Pays : International
Organisme : funding from State Key Laboratory of Organ Failure Research
ID : 201804
Pays : International
Organisme : THE award of Young Pearl Scholars of Guangdong province
ID : N/A
Pays : International
Informations de copyright
© 2018 by the American Association for the Study of Liver Diseases.