Plasma Metabolites Mediate the Associations of Gut Microbial Diversity with Ambulatory Blood Pressure and Its Variability.

Gut microbial richness (Chao1) was negatively associated with multiple blood pressure indices.

• Chao1 index was negatively associated with 24-hour systolic BP, daytime systolic BP, daytime diastolic BP, 24-hour systolic BPV, and nighttime systolic BPV (P < 0.05).
• Analyses were conducted on 523 Chinese participants from the MetaSalt study.
• Linear mixed models were used to characterize the relationships between α-diversity and BP indices.
• Both Shannon and Chao1 indices were examined as measures of α-diversity.

Twenty-six plasma metabolites were strongly associated with gut microbial richness (Chao1).

• 26 metabolites met the Bonferroni-corrected significance threshold (Bonferroni P < 0.05).
• Plasma targeted metabolomics was conducted on the 523 study participants.
• Metagenomics was used to assess gut microbial diversity.

Four key metabolites mediated the associations between gut microbial richness and blood pressure indices.

• The four mediating metabolites were imidazole propionate, 2-hydroxy-3-methylbutyric acid, homovanillic acid, and hydrocinnamic acid.
• Proportions of mediating effects ranged from 14.1% to 67.4%.
• Mediation analyses were performed to assess the contribution of metabolites to the observed associations between α-diversity and BP indices.

Hydrocinnamic acid was significantly associated with reduced risk of both prevalent and incident hypertension in a prospective cohort.

• Each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent hypertension (OR [95% CI] = 0.90 [0.82, 0.99]; P = 0.03).
• Each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of incident hypertension (HR [95% CI] = 0.83 [0.71, 0.96]; P = 0.01).
• These associations were evaluated in a prospective cohort of 2,169 participants.
• All four key metabolites were associated with hypertension in the prospective cohort.

Ambulatory blood pressure measurements were used to calculate 24-hour, daytime, and nighttime BP and blood pressure variability.

• BP variability (BPV) was derived from ambulatory BP measurements.
• Both systolic and diastolic BP indices across different time periods (24-hour, daytime, nighttime) were examined.
• The study population consisted of 523 Chinese participants from the MetaSalt study.