Lack of dietary fibre increases gut microbiome-derived uremic toxins that contribute to increased blood pressure

Insufficient dietary fibre intake is a known risk factor for high blood pressure and cardiovascular disease, yet its mechanistic basis remains unclear. Here, we identify a gut microbial pathway linking fibre deprivation to elevated blood pressure. In mice, low-fibre diets shifted microbial resource preference toward tyrosine fermentation, increasing host exposure to p-Cresol-derived metabolites, particularly p-Cresol glucuronide (PCG). Oral L-tyrosine, the precursor for p-Cresol, modestly increased PCG under normal fibre conditions, while antibiotics abolished it. In two healthy human cohorts, lower fibre intake was associated with higher PCG, which correlated with elevated blood pressure and co-expression with immune pathways. Mendelian Randomisation analysis supported a causal relationship between PCG and blood pressure. In a randomised controlled trial, fibre supplementation reduced both circulating PCG and blood pressure in individuals untreated for hypertension. These findings reveal a microbiota-mediated mechanism by which fibre deficiency promotes tyrosine fermentation and PCG production, contributing to elevated blood pressure.