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Reshaping commensal gut microbiota in early life lowers blood pressure potentially via a succinate mediated mechanism
Author(s) -
Chakraborty Saroj,
Galla Sarah,
Cheng Xi,
Yeo Ji-Youn,
Mell Blair,
Chiu Nathaline,
Wenceslau Camilla F.,
Kumar Matam Vijay,
Joe Bina
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06799
Subject(s) - amoxicillin , blood pressure , gut flora , offspring , medicine , physiology , antibiotics , firmicutes , endocrinology , pregnancy , immunology , biology , bacteria , microbiology and biotechnology , genetics , 16s ribosomal rna
Pediatric hypertension is recognized as an emerging global health concern. While 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 developmental stages of life affects blood pressure (BP) of pediatric subjects. To test this hypothesis, we administered amoxicillin (50mg/day/kg body weight with drinking water), the most commonly prescribed pediatric antibiotic, to alter gut microbiota of young, genetically hypertensive Dahl S rats (study 1) and dams during gestation and lactation to reshape microbiota of offspring (study 2). Reshaping of microbiota (determined by 16s sequencing), with reductions in Firmicutes/Bacteriodetes ratio observed in amoxicillin treated young rats and in dams. Amoxicillin treated rats (8 weeks old) also had lower blood pressure (radiotelemetry: 24‐hour average Systolic Blood Pressure in mmHg (SBP) : 155±2 * ) compared to the untreated rats (SBP : 166±3) (n=10–12/group). In the young rats treated with amoxicillin, the BP lowering effect persisted even after the antibiotics were discontinued (10 weeks old‐last 2 weeks without Amoxicillin) (amoxicillin SBP: 196±4 vs Control SBP: 231±10 * ). Similarly, offspring from the dams treated with amoxicillin also showed lower systolic blood pressure (SBP : 201±4 * ) compared to the control rats (SBP : 222±6) (9 weeks old and n=6–8/group) . 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 via choloremtric assay and found lower in animals treated with amoxicillin (410±33 mg/L * ) compared with control (508±30 mg/L). 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. Data presented as Mean±SEM. Non‐parametric Mann‐Whitney test*p<0.05. Support or Funding Information National Institutes of Health (R01HL143082)