Abstract 16278: Gut Microbiome Metabolic Phenotypes are Biomarkers for Severity of Myocardial Infarction
Intestinal microbiota have been mechanistically linked to myocardial infarction. We assessed the hypothesis that low molecular weight metabolites produced by intestinal microbiota and carried to the systemic circulation play a direct role in determining severity of myocardial infarction. Plasma from rats (n=8/group) treated for seven days with non-absorbed antibiotics vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin were analyzed using mass spectrometry. Hierarchical clustering of dissimilarities separated the levels of metabolites from treated vs. untreated rats. Of 284 identified metabolites, 193 were altered by the antibiotic treatments (p<0.05), with a tendency towards a decrease in metabolite levels. Amino acid catabolism was by far the most affected pathway with 50 metabolites significantly altered by one or both antibiotic treatments, 47 of which were significantly decreased (p<0.05).
Metabolites of the essential amino acids phenylalanine, tryptophan and tyrosine constituted the majority (33 of 50) of affected metabolites. Both antibiotic treatments decreased myocardial infarct size following 30 min in vitro ischemia/180 min reperfusion by 29% and 31%, from 49± 3% LV to 35± 3% LV and 34± 2% LV, respectively (p<0.05). We then determined whether the phenotype of decreased microbial metabolites of the essential amino acids phenylalanine (phenyllactate, phenylacetylglycine, phenylacetate, 3-phenylpropion[[Unable to Display Character: а]]te, and cinnamate), tryptophan (kynurenine, indoleacetate, indolepropionate, and 3-indoxyl sulfate) and tyrosine (p-cresol sulfate, phenol sulfate, 3-[4-hydroxyphenyl] lactate, and 4-hydroxyphenylpyruvate) were biomarkers of decreased severity of myocardial infarction. Rats treated with vancomycin were administered these metabolites intravenously or orally prior to ischemia/reperfusion studies. Oral or intravenous pretreatment with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin treatment. Administration of essential amino acid metabolites prior to ischemia/reperfusion had no effect on infarct size in untreated rats. We conclude gut microbiome metabolic phenotypes can serve as biomarkers for severity of myocardial infarction.
- © 2013 by American Heart Association, Inc.