Am J Clin Nutr. 2025 Jan 19:S0002-9165(25)00018-8. doi: 10.1016/j.ajcnut.2025.01.018. Online ahead of print.
ABSTRACT
BACKGROUND: Hippuric acid (HA), a host-microbe co-metabolite, normally derives from gut microbial catabolism of dietary polyphenols.
OBJECTIVES: We investigated the potential interplay between dietary polyphenols and gut microbiota on circulating HA levels, and examined the associations between serum concentrations of HA and cardiometabolic risk markers.
METHODS: In a 1-year cohort of 754 community-dwelling adults, serum HA and its precursor [benzoic acid (BA)] and fecal microbiota were assayed using liquid chromatography-tandem mass spectrometry and 16S ribosomal RNA sequencing, respectively. Diet, blood pressure, blood glucose and lipids were measured twice, 1-year apart. Arterial stiffness [indicated by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index] and liver fat accumulation [indicated by controlled attenuation parameter (CAP)] were measured after 1 year.
RESULTS: We identified 27 microbial genera whose relative abundance was positively associated with serum HA concentrations (PFDR<0.05) and constructed a microbial score to reflect the overall HA-producing potential. In multivariate-adjusted linear models, dietary intake of catechins and chlorogenic acids was positively associated with serum HA concentrations among participants with a higher microbial score (β=0.26, P=0.03), but not among those with a lower score (β=-0.13, P=0.30, Pinteraction=0.03). Participants with higher intake of dietary catechins and chlorogenic acids had lower triglyceride (Percentage change = -5.9%, P<0.05). Each 1 μmol/L increase in serum HA, but not in BA, was associated with 5.7%, 1.5%, 1.7%, 1.7%, and 1.7% decrease in triglyceride, systolic blood pressure, diastolic blood pressure, baPWV, and CAP, respectively (all P<0.05).
CONCLUSIONS: The gut microbial genera that predicted circulating HA levels may modify the association between dietary polyphenol intake and circulating HA levels, and elevated serum HA concentrations are favorably associated with multiple cardiometabolic risk markers.
PMID:39837385 | DOI:10.1016/j.ajcnut.2025.01.018