Abstract 14: Infant Gut Microbiome is Associated With Child Blood Pressure at Age 3 and 6 Years: Findings From a Danish Birth Cohort

Background: Experimental germ-free mice studies indicate that the gut microbiome affects blood pressure (BP). To our knowledge, no epidemiologic studies have investigated whether childhood BP, which portends future cardiovascular disease risk, is influenced by the infant gut microbiome—a microbiome that is less confounded by lifestyle. Understanding the link between gut microbiome and BP will shed light on gut microbiome as a modifiable way to improve child cardiovascular health. Objectives: To examine prospective associations of the gut microbiome at 1 month and 1 year with systolic BP (SBP) at 3 and 6 years, and to examine if the associations differed by breastfeeding duration over infancy. Methods: We used data from children followed up from birth to six years of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort in Denmark. We measured infant gut microbiome at 1mo and 1y by 16S rRNA sequencing (V4 region). Research staff measured child BP in triplicate using standardized protocols during scheduled study visits at 3y and 6y. We analyzed microbiome features at each time point during infancy in relation to SBP at 3y and 6y, separately. We focused on Shannon index as a measure of microbiome alpha diversity, and differential abundance of microbial taxa. We assessed effect measure modification by breastfeeding duration at time of microbiome measurement. We adjusted models for maternal diet score during pregnancy, preeclampsia, gestational age, birth weight, and breastfeeding duration (when it was not a modifier). Results: Of 526 children included in the analysis, 49% were female and 78% were born vaginally. A 1-unit increment in Shannon index at 1mo was associated with -0.35 mmHg (-1.61, 0.91) lower SBP at 3y and -1.21 (-2.20, -0.23) lower SBP at 6y. Lower abundance of Bacteroides and higher abundance of Staphylococcus at 1mo was associated with higher SBP at 3y only (both FDR-P <0.05); no microbial taxa at 1mo were significantly associated with SBP at 6y. As for microbiome at 1y, associations differed by breastfeeding duration ( P-interaction < 0.10). In children who were breastfed beyond 1y, a 1-unit increment in Shannon index at 1y was associated with -2.94 mmHg (-5.59, -0.28) and -1.02 mmHg (-3.24, 1.19) lower SBP at 3y (n=56) and 6y (n=72), respectively. In contrast, in children who were breastfed shorter than 1y, 1-unit increment in Shannon index was associated with 0.55 (-0.75, 1.85) and 1.26 (0.28, 2.24) higher SBP at 3y (n=298) and 6y (n=382), respectively. After multivariable adjustment, no microbial taxa at 1y were significantly associated with SBP at 3y or 6y. Conclusions: Higher gut microbiome Shannon diversity and higher Bacteroides and lower Staphylococcus at 1 month was prospectively associated with higher child BP at 3 and 6 years of age. Microbiome Shannon diversity at 1 year was also associated with child BP, however, associations depended on breastfeeding.