Related Experiment Video
Updated: Sep 15, 2026
Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
A surgical method for continuous intraportal infusion of gut microbial metabolites in mice
Danny Orabi1,2,3,4, Lucas J Osborn1,2,3, Kevin Fung1,2
1Department of Cardiovascular and Metabolic Sciences and.
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.
Insights
Researchers developed a new method to deliver gut microbial metabolites directly to the liver via the portal vein in mice. This technique allows for better study of how these metabolites affect health and disease.
Area of Science:
- Microbiology
- Physiology
- Metabolomics
Background:
- Gut microbes produce metabolites influencing human health and disease.
- Studying these microbial metabolites in animal models is challenging due to complex metabolic pathways.
- The liver is a primary site for metabolizing gut-derived compounds delivered via the portal vein.
Purpose of the Study:
- To develop and validate a novel technique for continuous portal vein infusion of gut microbial metabolites in mice.
- To investigate the physiological impact of specific microbial metabolites, trimethylamine (TMA) and 4-hydroxyphenylacetic acid (4-HPAA), using this new method.
Main Methods:
- A novel surgical technique involving portal vein cannulation and a subcutaneously implanted osmotic pump for continuous infusion in mice.
- Administration of trimethylamine (TMA) and 4-hydroxyphenylacetic acid (4-HPAA) via portal vein infusion.
- Analysis of peripheral plasma and hepatic metabolite levels, and hepatic gene expression using RNA-Seq.
Main Results:
- Continuous portal vein infusion of TMA led to increased peripheral plasma levels of TMA and its metabolite, trimethylamine-N-oxide.
- Intraportal administration of 4-HPAA resulted in elevated hepatic levels, while peripheral levels remained unchanged, confirming presystemic hepatic metabolism.
- RNA-Seq analysis revealed significant alterations in the hepatic transcriptome following 4-HPAA administration.
Conclusions:
- This study describes a novel and effective method for direct portal vein administration of gut microbial metabolites in mice.
- The technique accurately mimics physiological metabolite delivery, enabling robust investigation of their effects on liver physiology and gene expression.
- This method provides a valuable tool for mechanistic studies linking gut microbial metabolites to disease pathogenesis.
