TY - JOUR
T1 - p-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models
AU - Zhou, Yuyin
AU - Bi, Zheting
AU - Hamilton, Matthew J.
AU - Zhang, Li
AU - Su, Rui
AU - Sadowsky, Michael J.
AU - Roy, Sabita
AU - Khoruts, Alexander
AU - Chen, Chi
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/10
Y1 - 2023/10
N2 - Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.
AB - Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.
KW - antibiotics
KW - aromatic amino acid
KW - fecal microbiota transplantation
KW - gut microbiota
KW - metabolomics
KW - microbial metabolism
KW - p-cresol sulfate
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U2 - 10.3390/ijms241914621
DO - 10.3390/ijms241914621
M3 - Article
C2 - 37834066
AN - SCOPUS:85174466889
SN - 1661-6596
VL - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 14621
ER -