What question did this study set out to answer?

The aim is to assess the capacity for individual production of phenyl sulfate through an oral tyrosine test.

June 5, 2026npj Metabolic Health and Disease0 citationsOpen Access

An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production

TLTing‐Yun Lin SHSzu-Chun Hung TATakaaki Abe

Key Points

The aim is to assess the capacity for individual production of phenyl sulfate through an oral tyrosine test.
Developed an oral tyrosine challenge test (OTyCT) for assessing phenyl sulfate production.
Forty-eight healthy adults underwent a standardized tyrosine load with plasma phenyl sulfate levels measured at 48 hours using LC-MS.
Defined high-phenyl sulfate producers based on the incremental area under the curve (AUC) of phenyl sulfate concentrations.
Substantial interindividual variability in phenyl sulfate production was observed, independent of baseline levels.
Sixteen participants categorized as high-phenyl sulfate producers exhibited unique gut microbial signatures.
High-phenyl sulfate producers had comparable abundances of phenol-biosynthetic genes and SULT1A1 genotypes.

Abstract

Phenyl sulfate (PS), a gut microbiota-derived metabolite implicated in the pathogenesis of diabetic kidney disease, is generated through microbial conversion of dietary tyrosine to phenol, followed by hepatic sulfation via SULT1A1. We developed an oral tyrosine challenge test (OTyCT) to phenotype individual PS-producing capacity. Forty-eight healthy adults underwent a standardized tyrosine load with serial plasma PS levels measured over 48 h using LC-MS. OTyCT revealed substantial interindividual variability of PS production independent of baseline PS levels, highlighting marked heterogeneity in host-microbiome metabolic interactions. Sixteen participants in the highest tertile of the incremental area under the curve of PS were defined as high-PS producers. High PS producers exhibited distinct gut microbial signatures despite comparable abundances of known phenol-biosynthetic genes and host SULT1A1 genotypes. These findings suggest that susceptibility to PS-related complications may vary according to gut microbial profiles, supporting OTyCT as a practical tool for metabolic phenotyping and microbiome-informed precision nutrition. Clinical Trial registry name and registration number: Identification of P-Cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome, NCT04204174.

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