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

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

doi:10.1080/19490976.2018.1502536

Cited by 19 publications

(10 citation statements)

References 36 publications

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“…Previous studies have found associations between urinary N3-IS levels and the microbiota composition. In particular, the relative abundance of bacteria from the class Clostridia was positively associated with N3-IS, whereas Bacilli were negatively associated with N3-IS 16,17 . As Clostridia have been associated with a decreased and Bacilli with an increased CDI risk, we hypothesized that patients with a low N3-IS level would be at an increased risk of CDI [18][19][20][21] .…”

Section: Discussionmentioning

confidence: 97%

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

et al. 2021

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Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk.

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Section: Discussionmentioning

confidence: 97%

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

et al. 2021

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“…Transplanting Clostridium to germ-free nutrition-deficient mice can increase the acylcarnitine level in the gut and decrease protein synthesis and amino acid oxidation in the liver (Blanton et al, 2016 ), thereby promoting the development of cancer. Clostridiumalos difficile , as a member of the Clostridiales class, also plays a pivotal role in regulating Clostridium difficile infections (CDI) (Farowski et al, 2019 ). The Gram-negative Pseudomonas is over-represented in cases of oral squamous cell carcinoma (OSCC) (Perera et al, 2018 ), a kind of tumor that is similar to ESCC.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Esophageal Microbiota and Prediction of the Metabolic Pathways Involved in Esophageal Cancer

Hou

et al. 2020

Front. Cell. Infect. Microbiol.

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Esophageal microbiota plays important roles in esophageal cancer. Esophagectomy, as the most important therapeutic way, contributes to changes of esophageal microbiome. However, there are few studies examining the esophageal microbiome and the metabolic changes before and after esophagectomy. The present study characterized the esophageal microbiome of 17 patients with esophageal squamous cell carcinoma (ESCC), 11 patients with esophagogastric junction (EGJ) cancer, 15 patients at 9-12 months after radical esophagectomy and 16 healthy controls (HC). 16S ribosomal RNA gene sequencing was used to evaluate the microbiome and predict the metabolic pathways. Our results showed that the microbial diversity was significantly lower in ESCC, EGJ and post-ESCC groups than that in the HC group. The abundance of Fusobacteria was higher (7.01 vs. 1.12%, P = 0.039) and the abundance of Actinobacteria (1.61 vs. 4.04%) was lower in the ESCC group than that in the HC group. We found significant differences in the abundance of Bacteroidetes (20.45 vs. 9.86%, P = 0.026), Fusobacteria (7.01 vs. 1.66%, P = 0.030) between ESCC and post-ESCC groups. The results of microbial composition analysis and PICRUSt demonstrated significant differences between ESCC and HC groups. The β diversity and PICRUSt suggested that the microbial composition and metabolic pathways were similar to HC group after esophagectomy. The monitoring of the esophagus microbiota may be an essential method to predict the recurrence of tumor.

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“…In a subsample (n = 855) of individuals with minimal renal decline, serum indoxyl sulfate and p-cresol sulfate were both associated with the presence of family members of Clostridiales in the GMB [ 184 ]. More recently, in a study of mixed inpatients treated clinically with antibiotics, uri-nary indoxyl levels were found to be associated with the relative abundance of Clostridiales [ 168 ]. Thus, our own data would suggest that the broad-spectrum antibiotic suppressed at the very least, members of the Clostridia family.…”

Section: Discussionmentioning

confidence: 99%

“…The available literature supports several generalizations. Most antibiotic-treatment regimens lower the overall diversity of the GMB [14,[167][168][169][170]. Furthermore, antibiotic class-specific effects on the GMB architecture have been well demonstrated [8][9][10][11].…”

Section: Associations With Specific Gut Microbiotamentioning

confidence: 99%

Changes in the Serum Metabolome of Patients Treated With Broad-Spectrum Antibiotics

Jaskiw

Obrenovich

Kundrapu

et al. 2020

PAI

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Background: The gut microbiome (GMB) generates numerous small chemicals that can be absorbed by the host and variously biotransformed, incorporated, or excreted. The resulting metabolome can provide information about the state of the GMB, of the host, and of their relationship. Exploiting this information in the service of biomarker development is contingent on knowing the GMB-sensitivity of the individual chemicals comprising the metabolome. In this regard, human studies have lagged far behind animal studies. Accordingly, we tested the hypothesis that serum levels of chemicals unequivocally demonstrated to be GMB-sensitive in rodent models would also be affected in a clinical patient sample treated with broad spectrum antibiotics.Methods: We collected serum samples from 20 hospitalized patients before, during, and after treatment with broad-spectrum antibiotics. We also collected samples from 5 control patients admitted to the hospital but not prescribed antibiotics. We submitted the samples for a non-targeted metabolomic analysis and then focused on chemicals known to be affected both by germ-free status and by antibiotic treatment in the mouse and/or rat.Results: Putative identification was obtained for 499 chemicals in human serum. An aggregate analysis did not show any time x treatment interactions. However, our literature search identified 10 serum chemicals affected both by germ-free status and antibiotic treatment in the mouse or rat. Six of those chemicals were measured in our patient samples and additionally met criteria for inclusion in a focused analysis. Serum levels of 5 chemicals (p-cresol sulfate, phenol sulfate, hippurate, indole propionate, and indoxyl sulfate) declined significantly in our group of antibiotic-treated patients but did not change in our patient control group.Conclusions: Broad-spectrum antibiotic treatment in patients lowered serum levels of selected chemicals previously demonstrated to be GMB-sensitive in rodent models. Interestingly, all those chemicals are known to be uremic solutes that can be derived from aromatic amino acids (L-phenylalanine, L-tyrosine, or L-tryptophan) by anaerobic bacteria, particularly Clostridial species. We conclude that judiciously selected serum chemicals can reliably detect antibiotic-induced suppression of the GMB in man and thus facilitate further metabolome-based biomarker development.

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

Abstract: In conjunction with patient antibiotic history, 3-IS is a candidate marker to predict RAC.

Cited by 19 publications

References 36 publications

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Characterization of the Esophageal Microbiota and Prediction of the Metabolic Pathways Involved in Esophageal Cancer

Changes in the Serum Metabolome of Patients Treated With Broad-Spectrum Antibiotics

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