Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats

Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days wi...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one 2016-08, Vol.11 (8), p.e0160840
Main Authors:	Lam, Vy, Su, Jidong, Hsu, Anna, Gross, Garrett J, Salzman, Nita H, Baker, John E
Format:	Article
Language:	eng
Subjects:	1-Phosphatidylinositol 3-kinase AKT protein Amino acids Animals Anti-Bacterial Agents - pharmacology Antibiotics Bacitracin Biology and Life Sciences Cardiovascular disease Cardiovascular diseases Catabolism Cell surface Cell survival Channels Cluster analysis Clustering Diabetes Diagnosis Diagnostic systems Dosage and administration Drug therapy Gastrointestinal Microbiome - drug effects Glibenclamide Heart attack Heart attacks Heart surgery Hypotheses Hypothesis testing In vivo methods and tests Infarction Intestinal microflora Intestine Intravenous administration Ischemia Kinases Low molecular weights MAP kinase Mass spectrometry Mass spectroscopy Medicine and Health Sciences Metabolism Metabolites Metabolomics Microbiota Microbiota (Symbiotic organisms) Microorganisms Molecular weight Myocardial infarction Myocardial Infarction - metabolism Myocardial Infarction - microbiology Neomycin Patient outcomes Pharmacology Phenotype Phenylalanine Physiological aspects Polymyxin B Pretreatment Probiotics Proteins Rats Receptors Reperfusion Scientific imaging Streptomycin Studies Toxicology Tryptophan Tyrosine Vancomycin Vancomycin - pharmacology Wortmannin
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host's metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in untreated rats. This study links gut microbiota metabolites to severity of myocardial infarction and may provide future opportunities for novel diagnostic tests and interventions for the prevention of cardiovascular disease.
ISSN:	1932-6203 1932-6203