Associations of the gut microbiome and cardiometabolic risk in adolescence: the HOME study

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BACKGROUND: Alterations to the gut microbiome have been linked to cardiometabolic disease, like type 2 diabetes and hypertension, in adults, but few studies have investigated these associations in adolescents. We examined the relation between the gut microbiome and cardiometabolic risk in adolescence and determined whether sex and race/ethnicity modified these associations. METHODS: In 144 adolescents (age range: 11–14 years) from the Health Outcomes and Measures of the Environment (HOME) Study, we quantified gut microbiome alpha diversity using the Shannon index and species’ relative abundances (i.e., centered log-ratio normalized abundances) in stool DNA that underwent metagenomic sequencing. We assessed adolescent cardiometabolic risk using a cardiometabolic risk summary score, its individual components (i.e., visceral fat, leptin to adiponectin ratio, HOMA-IR, triglyceride to high-density lipoprotein cholesterol ratio, and systolic blood pressure), as well as total cholesterol and hemoglobin A1c. We used linear regression models to estimate covariate-adjusted cross-sectional associations of the Shannon diversity index and species’ relative abundances with cardiometabolic risk, and examine differences in these associations by sex and race/ethnicity. At the species level, the false discovery rate (FDR) correction, with q-value < 0.20, was considered statistically significant. RESULTS: Among all adolescents, a higher Shannon diversity index was associated with lower systolic blood pressure [β: -0.18 (95% CI: -0.35, -0.01)] in covariate-adjusted models. However, the associations of the Shannon diversity index with cardiometabolic risk did not differ significantly by sex or race/ethnicity. Although associations of the relative abundances of species, prevalent in at least 10% of samples, with cardiometabolic risk were not statistically significant tamong all adolescents after correcting for multiple comparisons (qFDR ≥ 0.20), sex modified the association of the relative abundance of Ruminococcus lactaris with HOMA-IR (qinteraction = 0.151), with positive association among females [β: 2.05 (95% CI: 0.93, 3.17), q = 0.155] and suggestive negative association among males [β: -0.84 (95% CI: -1.59, -0.09), q = 0.983]. Associations of the relative abundances of Streptococcus parasanguinis (qinteraction = 0.097), Enterocloster SGB14313 (qinteraction = 0.097), and Alistipes ihumii (qinteraction = 0.097) with total cholesterol also differed between female and male adolescents. We observed differences between adolescents of non-Hispanic black and non-Hispanic white race/ethnicity in the association of the relative abundance of Lachnospira pectinoschiza (qinteraction = 0.028) with total cholesterol. CONCLUSIONS: Our findings suggest that the gut microbiome is associated with cardiometabolic risk in adolescence in a sex-specific manner, and may differ by race and ethnicity.

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