Exposure to Amoxicillin in Early Life Is Associated With Changes in Gut Microbiota and Reduction in Blood Pressure: Findings From a Study on Rat Dams and Offspring

Autor: Saroj Chakraborty, Blair Mell, Sarah Galla, Jiyoun Yeo, Matam Vijay-Kumar, Camilla F Wenceslau, Xi Cheng, Nathaline Chiu, Bina Joe
Rok vydání: 2020
Předmět:
Male
Antibiotics
Succinic Acid
Physiology
Blood Pressure
Veillonellaceae
030204 cardiovascular system & hematology
Gut flora
pediatric hypertension
0302 clinical medicine
Pregnancy
Lactation
Mechanisms
Original Research
0303 health sciences
biology
Incidence (epidemiology)
Age Factors
Anti-Bacterial Agents
medicine.anatomical_structure
Maternal Exposure
Prenatal Exposure Delayed Effects
Hypertension
Gestation
Female
Cardiology and Cardiovascular Medicine
medicine.drug
Offspring
medicine.drug_class
metabolite
Gestational Age
03 medical and health sciences
medicine
Animals
030304 developmental biology
Rats
Inbred Dahl
gut microbiota
business.industry
Amoxicillin
biology.organism_classification
Gastrointestinal Microbiome
maternal
Disease Models
Animal
Blood pressure
Animal Models of Human Disease
High Blood Pressure
business
Basic Science Research
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
DOI: 10.1161/jaha.119.014373
Popis: Background Pediatric hypertension is recognized as an emerging global health concern. Although new guidelines are developed for facilitating clinical management, the reasons for the prevalence of hypertension in children remain unknown. Genetics and environmental factors do not fully account for the growing incidence of pediatric hypertension. Because stable bacterial flora in early life are linked with health outcomes later in life, we hypothesized that reshaping of gut microbiota in early life affects blood pressure ( BP ) of pediatric subjects. Methods and Results To test this hypothesis, we administered amoxicillin, the most commonly prescribed pediatric antibiotic, to alter gut microbiota of young, genetically hypertensive rats (study 1) and dams during gestation and lactation (study 2) and recorded their BP . Reshaping of microbiota with reductions in Firmicutes/Bacteriodetes ratio were observed. Amoxicillin treated rats had lower BP compared with untreated rats. In young rats treated with amoxicillin, the lowering effect on BP persisted even after antibiotics were discontinued. Similarly, offspring from dams treated with amoxicillin showed lower systolic BP compared with control rats. Remarkably, in all cases, a decrease in BP was associated with lowering of Veillonellaceae, which are succinate‐producing bacteria. Elevated plasma succinate is reported in hypertension. Accordingly, serum succinate was measured and found lower in animals treated with amoxicillin. Conclusions Our results demonstrate a direct correlation between succinate‐producing gut microbiota and early development of hypertension and indicate that reshaping gut microbiota, especially by depleting succinate‐producing microbiota early in life, may have long‐term benefits for hypertension‐prone individuals.
Databáze: OpenAIRE
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