Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding

Background Germ‐free mice experiments indicate that human gut microbiota influence blood pressure (BP), but no studies have prospectively examined if infant gut microbiota affects their future childhood BP. We aim to investigate prospective associations of infant gut microbiota diversity and composi...

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Main Authors: Tiange Liu, Jakob Stokholm, Mingyu Zhang, Rebecca Vinding, Søren J. Sørensen, Ni Zhao, Noel T. Mueller
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.037447
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author Tiange Liu
Jakob Stokholm
Mingyu Zhang
Rebecca Vinding
Søren J. Sørensen
Ni Zhao
Noel T. Mueller
author_facet Tiange Liu
Jakob Stokholm
Mingyu Zhang
Rebecca Vinding
Søren J. Sørensen
Ni Zhao
Noel T. Mueller
author_sort Tiange Liu
collection DOAJ
description Background Germ‐free mice experiments indicate that human gut microbiota influence blood pressure (BP), but no studies have prospectively examined if infant gut microbiota affects their future childhood BP. We aim to investigate prospective associations of infant gut microbiota diversity and composition with childhood BP, examining effect measure modification by breastfeeding and mediation by a child's body mass index. Methods and Results In the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort, we measured infant gut microbiota (16S rRNA V4) at 1 week, 1 month, and 1 year and child BP at 3 and 6 years. We assessed α diversity‐BP, β diversity‐BP, and microbe abundances‐BP associations using linear regression, permutational multivariate analysis of variance, and beta‐binomial count regression, respectively. Data from 526 children showed that α diversity and several Bifidobacterium spp. had protective associations with BP but only in children breastfed for ≥6 months. For instance, a 1‐unit increment in 1 month Shannon index was associated with 1.86 mm Hg (95% CI, 0.66–3.05) lower 6‐year systolic BP in children breastfed ≥6 months but a 0.73 (95% CI, −1.00 to 2.45) higher 6‐year systolic BP in those breastfed <6 months (P‐interaction=0.02). Greater abundance of 2 Bifidobacterium microbes at 1 week was negatively associated with 6‐year systolic BP when breastfeeding ≥6 months (P‐interaction<0.1). Further, abundance of 8 microbes at 1week or 1 month was linked to 3‐year or 6‐year BP (false discovery rate P<0.05), with 5 of them independent of a child's body mass index. Lastly, 1‐week unweighted UniFrac distance and 1‐year weighted UniFrac distance were associated with BP after adjustment (P<0.05). Conclusions Gut microbiota features at 1 week and 1 month of life were associated with BP at 6 years. Breastfeeding duration modified key associations including those for α diversity and Bifidobacteria.
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spelling doaj-art-75be33348d1d4e64bb286cb3f228c04a2025-08-20T02:25:02ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-03-0114510.1161/JAHA.124.037447Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of BreastfeedingTiange Liu0Jakob Stokholm1Mingyu Zhang2Rebecca Vinding3Søren J. Sørensen4Ni Zhao5Noel T. Mueller6Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USACopenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital University of Copenhagen DenmarkDepartment of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USACopenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital University of Copenhagen DenmarkSection of Microbiology University of Copenhagen Copenhagen DenmarkDepartment of Biostatistics Johns Hopkins Bloomberg School of Public Health Baltimore MD USADepartment of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USABackground Germ‐free mice experiments indicate that human gut microbiota influence blood pressure (BP), but no studies have prospectively examined if infant gut microbiota affects their future childhood BP. We aim to investigate prospective associations of infant gut microbiota diversity and composition with childhood BP, examining effect measure modification by breastfeeding and mediation by a child's body mass index. Methods and Results In the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort, we measured infant gut microbiota (16S rRNA V4) at 1 week, 1 month, and 1 year and child BP at 3 and 6 years. We assessed α diversity‐BP, β diversity‐BP, and microbe abundances‐BP associations using linear regression, permutational multivariate analysis of variance, and beta‐binomial count regression, respectively. Data from 526 children showed that α diversity and several Bifidobacterium spp. had protective associations with BP but only in children breastfed for ≥6 months. For instance, a 1‐unit increment in 1 month Shannon index was associated with 1.86 mm Hg (95% CI, 0.66–3.05) lower 6‐year systolic BP in children breastfed ≥6 months but a 0.73 (95% CI, −1.00 to 2.45) higher 6‐year systolic BP in those breastfed <6 months (P‐interaction=0.02). Greater abundance of 2 Bifidobacterium microbes at 1 week was negatively associated with 6‐year systolic BP when breastfeeding ≥6 months (P‐interaction<0.1). Further, abundance of 8 microbes at 1week or 1 month was linked to 3‐year or 6‐year BP (false discovery rate P<0.05), with 5 of them independent of a child's body mass index. Lastly, 1‐week unweighted UniFrac distance and 1‐year weighted UniFrac distance were associated with BP after adjustment (P<0.05). Conclusions Gut microbiota features at 1 week and 1 month of life were associated with BP at 6 years. Breastfeeding duration modified key associations including those for α diversity and Bifidobacteria.https://www.ahajournals.org/doi/10.1161/JAHA.124.037447Bifidobacteriabreastfeedingchildhood blood pressureearly‐life gut microbiota
spellingShingle Tiange Liu
Jakob Stokholm
Mingyu Zhang
Rebecca Vinding
Søren J. Sørensen
Ni Zhao
Noel T. Mueller
Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Bifidobacteria
breastfeeding
childhood blood pressure
early‐life gut microbiota
title Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding
title_full Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding
title_fullStr Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding
title_full_unstemmed Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding
title_short Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding
title_sort infant gut microbiota and childhood blood pressure prospective associations and the modifying role of breastfeeding
topic Bifidobacteria
breastfeeding
childhood blood pressure
early‐life gut microbiota
url https://www.ahajournals.org/doi/10.1161/JAHA.124.037447
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