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A surgical method for continuous intraportal infusion of gut microbial metabolites in mice.
- Source :
-
JCI insight [JCI Insight] 2021 May 10; Vol. 6 (9). Date of Electronic Publication: 2021 May 10. - Publication Year :
- 2021
-
Abstract
- Gut microbe-derived metabolites influence human physiology and disease. However, establishing mechanistic links between gut microbial metabolites and disease pathogenesis in animal models remains challenging. The major route of absorption for microbe-derived small molecules is venous drainage via the portal vein to the liver. In the event of presystemic hepatic metabolism, the route of metabolite administration becomes critical. To our knowledge, we describe here a novel portal vein cannulation technique using a s.c. implanted osmotic pump to achieve continuous portal vein infusion in mice. We first administered the microbial metabolite trimethylamine (TMA) over 4 weeks, during which increased peripheral plasma levels of TMA and its host liver-derived cometabolite, trimethylamine-N-oxide, were observed when compared with a vehicle control. Next, 4-hydroxyphenylacetic acid (4-HPAA), a microbial metabolite that undergoes extensive presystemic hepatic metabolism, was administered intraportally to examine effects on hepatic gene expression. As expected, hepatic levels of 4-HPAA were elevated when compared with the control group while peripheral plasma 4-HPAA levels remained the same. Moreover, significant changes in the hepatic transcriptome were revealed by an unbiased RNA-Seq approach. Collectively, to our knowledge this work describes a novel method for administering gut microbe-derived metabolites via the portal vein, mimicking their physiologic delivery in vivo.
- Subjects :
- Animals
Gene Expression drug effects
Methylamines blood
Methylamines metabolism
Methylamines pharmacology
Mice
Phenylacetates blood
Phenylacetates metabolism
Phenylacetates pharmacology
RNA-Seq
Transcriptome drug effects
Gastrointestinal Microbiome
Infusions, Intravenous methods
Liver metabolism
Methylamines administration & dosage
Phenylacetates administration & dosage
Portal Vein
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 6
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 33986195
- Full Text :
- https://doi.org/10.1172/jci.insight.145607