Associations between diet, metabolome, gut microbiota and blood pressure in Australian adults.

PURPOSE: Early metabolomic and microbial markers of blood pressure (BP) dysregulation may be detectable before clinical hypertension develops. This exploratory study aimed to examine associations among dietary intake, BP, metabolomic profiles (plasma and urine), and gut microbiota composition. A secondary aim was to assess whether circulating metabolites mediate relationships between significant dietary factors and BP.

METHOD: This was a cross-sectional analysis of baseline data from a randomised cross-over trial. Usual dietary intake was assessed using the Australian Eating Survey (AES)® - Heart version Food Frequency Questionnaire. In-clinic BP measurements were measured and participants provided plasma, urine, and stool samples. Plasma and urine were analysed via untargeted metabolomics. Stool samples were collected for shotgun metagenomic sequencing, though metagenomic data was not included in this analysis. Associations between BP, individual metabolites, microbial taxa, and alpha diversity were assessed using linear regression with false discovery rate (FDR) correction. Causal mediation analysis was performed using nonparametric bootstrapping.

RESULT: Thirty-four Australian adults (mean age: 38.4 ± 18.1 years; 52.9% female) had complete data at baseline. Nut intake (servings/day and % energy) was the only dietary factor significantly associated with systolic BP (SBP), with higher intake linked to a 1.13 mmHg reduction. Twenty-nine plasma lipid metabolites were significantly associated with SBP after FDR correction. Of these, nine lipid-related metabolites, particularly 1,2-dilinoleoyl-GPC (18:2/18:2) and 1-linoleoyl-GPC (18:2), were observed to partially mediate the nut-SBP relationship. No urinary metabolites or microbial taxa were significantly associated with BP.

CONCLUSIONS

In this exploratory cross-sectional study, specific lipid metabolites were associated with SBP and partly accounted for the nut-SBP association. These hypothesis-generating findings suggest potential biomarkers of nut intake and BP regulation, warranting confirmation in larger longitudinal, interventional, and mechanistic studies.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (Registration number ACTRN12622001321730, Registration date 12/10/2022).