title: Intestinal microbiota determine severity of myocardial infarction in rats.
abstract: Signals from the intestinal microbiota are important for normal host physiology; alteration of the microbiota (dysbiosis) is associated with multiple disease states. We determined the effect of antibiotic-induced intestinal dysbiosis on circulating cytokine levels and severity of ischemia/reperfusion injury in the heart. Treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin, in the drinking water, decreased circulating leptin levels by 38%, resulted in smaller myocardial infarcts (27% reduction), and improved recovery of postischemic mechanical function (35%) as compared with untreated controls. Vancomycin altered the abundance of intestinal bacteria and fungi, measured by 16S and 18S ribosomal DNA quantity. Pretreatment with leptin (0.12 μg/kg i.v.) 24 h before ischemia/reperfusion abolished cardioprotection produced by vancomycin treatment. Dahl S rats fed the commercially available probiotic product Goodbelly, which contains the leptin-suppressing bacteria Lactobacillus plantarum 299v, also resulted in decreased circulating leptin levels by 41%, smaller myocardial infarcts (29% reduction), and greater recovery of postischemic mechanical function (23%). Pretreatment with leptin (0.12 μg/kg i.v.) abolished cardioprotection produced by Goodbelly. This proof-of-concept study is the first to identify a mechanistic link between changes in intestinal microbiota and myocardial infarction and demonstrates that a probiotic supplement can reduce myocardial infarct size.
authors.affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Vy
authors.initials: V
authors.lastname: Lam
authors.forename: Jidong
authors.initials: J
authors.lastname: Su
authors.forename: Stacy
authors.initials: S
authors.lastname: Koprowski
authors.forename: Anna
authors.initials: A
authors.lastname: Hsu
authors.forename: James S
authors.initials: JS
authors.lastname: Tweddell
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Rafiee
authors.forename: Garrett J
authors.initials: GJ
authors.lastname: Gross
authors.forename: Nita H
authors.initials: NH
authors.lastname: Salzman
authors.forename: John E
authors.initials: JE
authors.lastname: Baker
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D060766:Drinking Water; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D054892:Metagenome / Q000187:drug effects*; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D019936:Probiotics / Q000627:therapeutic use; D051381:Rats; D020303:Rats, Inbred Dahl; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D060766:Drinking Water; D020738:Leptin; D014640:Vancomycin