Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

Abstract

Reduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health.

Investigation of Variations in the Human Urine Metabolome amongst European Populations: An Exploratory Search for Biomarkers of People at Risk‐of‐Poverty

“…The signals from citrate and hippurate appeared to be higher in the AFF cohort. As stated above, an increased hippurate concentration in urine has been linked to a high consumption of foods like fruit and vegetables, dark chocolate, fruit, and whole grains, that may not be affordable for ROP subjects.…”

The renal transport of hippurate and protein‐bound solutes

“…These subjects, whose serum creatinine concentrations were 1.28, 0.72, and 0.84 mg/dl, respectively, had plasma concentrations of hippurate substantially greater than those in the rest of the study group. It is known that plasma hippurate concentration is influenced by dietary factors and by gut microbiome composition (Pallister et al, ). It seems likely that the observed reduced hippurate clearance seen in these three patients is related to their higher plasma hippurate concentration.…”

Diet‐derived microbial metabolites in health and disease

“…; Pallister et al . ). Mean 24‐hour urinary excretion of this metabolite has been associated with lower blood pressure (Holmes et al .…”

“…; Pallister et al . ) and intake of coffee, fruit, dietary fibres and wholegrains (Holmes et al . ; Heinzmann et al .…”

“…Some of the microbial-derived metabolites of polyphenols may affect the host's metabolism leading to improved health, although direct evidence is still lacking. One example is hippuric acid, a microbial-derived metabolite associated with gut microbial diversity (Roager et al 2016;Pallister et al 2017) and intake of coffee, fruit, dietary fibres and wholegrains (Holmes et al 2008;Heinzmann et al 2012;Pallister et al 2017). Mean 24-hour urinary excretion of this metabolite has been associated with lower blood pressure (Holmes et al 2008) and increased fasting serum hippuric acid following bilberry consumption has been associated with improvements in fasting plasma glucose levels and insulin secretion (de Mello et al 2017a(de Mello et al , 2017b.…”