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Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales

Fedja Farowski, Gregor Els, Anastasia Tsakmaklis, Paul G Higgins, Christian R. Kahlert, Christoph K Stein-Thoeringer, Johanna S Bobardt, Katja Dettmer-Wilde, Peter J Oefner, Jörg Janne Vehreschild & Maria J G T Vehreschild

abstract

OBJECTIVES
After allogeneic hematopoietic stem cell transplantation (allo-HCT), urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance of bacteria from the class Clostridia (RAC), and antibiotic treatment is considered the major determinant of this outcome. A high RAC has been associated with favorable outcome after allo-HCT and protection from Clostridium difficile infection (CDI). We assessed correlations between alpha diversity, RAC and urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated patients to further explore 3-IS as a biomarker of reduced diversity and predisposition to CDI.

METHODS
Fecal and urinary specimens were analyzed from 40 non-allo-HCT hospitalized patients before and 9 ± 2 days after initiation of intravenous antibiotic treatment. Fecal microbiota were analyzed by 16s RNA sequencing and urinary 3-IS was analyzed by liquid chromatography-tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of 3-IS.

RESULTS
At a RAC cutoff of <30%, the binary logarithm of 3-IS (medium 3-IS: ≤2.5; high 3-IS: >2.5) was predictive with an accuracy of 82% (negative predictive value: 87%, positive predictive value 67%). Accuracy was improved by combing antibiotic history with 3-IS levels (accuracy 89%, npv 88%, ppv 92%).

CONCLUSION
In conjunction with patient antibiotic history, 3-IS is a candidate marker to predict RAC.
   
citation Farowski F, Els G, Tsakmaklis A, Higgins P G, Kahlert C R, Stein-Thoeringer C K, Bobardt J S, Dettmer-Wilde K, Oefner P J, Vehreschild J J, Vehreschild M J G T. Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales. Gut Microbes 2018;1-9.
   
type journal paper/review (English)
date of publishing 17-08-2018
journal title Gut Microbes
ISSN electronic 1949-0984
pages 1-9
PubMed 30118620
DOI 10.1080/19490976.2018.1502536