#1172 Identification of phenyl sulfate producer phenotypes by an oral tyrosine challenge test: a microbiota-based personalized nutritional approach

Abstract

Abstract Background and Aims Phenyl sulfate (PS) has been implicated in the pathogenesis of diabetic kidney disease (DKD). PS is converted from phenol, a gut microbial metabolite of dietary tyrosine, and sulfated into PS by aryl sulfotransferases in the host liver. We hypothesized that the effects of a particular diet on metabolic responses might differ from person to person. In the present study, we aimed to characterize various PS producer phenotypes using an oral tyrosine challenge test (TCT). Method We developed the TCT to determine the individual PS producing capacity. Plasma samples were collected at baseline after overnight fasting, and were then collected at 4, 8, 12, 24, 36 and 48 hours after oral administration of L-tyrosine at a dose of 100 mg/kg. PS concentrations were measured by high performance liquid chromatography. The gut microbiome was assessed by metagenomic shotgun sequencing. Results A total of 48 healthy volunteers were enrolled to undergo the TCT. The mean age of the participants was 32 ± 8 years; 50% were men, and 50% were vegetarians. The time-concentration curves of PS were similar among the participants, with the maximal increase of PS at the 24th hour (Fig. A). Participants were stratified into tertiles according to the PS levels at the 24th hour after the TCT. The 16 participants in the highest tertile were defined as high-PS producers, whereas those in the lowest tertile were defined as low-PS producers (Fig. B). We found that there was no difference in age, gender, dietary habit, BMI, eGFR, and baseline plasma PS levels between the 2 groups. However, the high-PS producers had higher levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol. In addition, distinct differences in gut microbial composition were identified. At the species level, the relative abundance of Alistipes dispar, Clostridium sp. C5-48, and Butyricimonas faecihominis was markedly increased in the high-PS producers (Fig. C). Conclusion We found high PS variability in the response to a TCT, suggesting that universal dietary recommendations may have limited utility in reducing PS levels. Further studies are warranted to investigate the potential clinical applications of the TCT in patients with DKD.