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Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection

Microbiome-based therapeutics are increasingly evaluated as a strategy to reduce recurrent Clostridioides difficile infection (rCDI), with proposed mechanisms including restoration of the microbiota and microbiota-mediated functions, such as bile acid (BA) metabolism. This study reports a quantitati...

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Detalles Bibliográficos
Autores principales: Papazyan, Romeo, Ferdyan, Nicky, Srinivasan, Karthik, Gonzalez, Carlos, Shannon, William D., Blount, Ken, Fuchs, Bryan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865816/
https://www.ncbi.nlm.nih.gov/pubmed/36677428
http://dx.doi.org/10.3390/microorganisms11010135
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author Papazyan, Romeo
Ferdyan, Nicky
Srinivasan, Karthik
Gonzalez, Carlos
Shannon, William D.
Blount, Ken
Fuchs, Bryan C.
author_facet Papazyan, Romeo
Ferdyan, Nicky
Srinivasan, Karthik
Gonzalez, Carlos
Shannon, William D.
Blount, Ken
Fuchs, Bryan C.
author_sort Papazyan, Romeo
collection PubMed
description Microbiome-based therapeutics are increasingly evaluated as a strategy to reduce recurrent Clostridioides difficile infection (rCDI), with proposed mechanisms including restoration of the microbiota and microbiota-mediated functions, such as bile acid (BA) metabolism. This study reports a quantitative and sensitive assay for targeted metabolomic assessment, and the application of the assay to profile BA composition in a Phase 2 trial of the investigational microbiota-based live biotherapeutic RBX2660 for reduction of rCDI. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 35 BAs from 113 participant stool samples from 27 RBX2660-treated rCDI participants in the double-blinded, placebo-controlled clinical trial. The results demonstrate a high-confidence assay as represented by sensitivity, linearity, accuracy, and precision. Furthermore, the assay enabled the observation of primary BAs as the dominant BA species at baseline in stool samples from clinical trial participants, consistent with the expected loss of commensals after broad-spectrum antibiotic treatment. After RBX2660 administration, there was a significant drop in primary BAs concurrent with increased secondary BAs that sustained through 24 months post-RBX2660. Taken together, we describe a robust assay that demonstrates altered BA metabolism in rCDI patients treated with RBX2660 administration.
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spelling pubmed-98658162023-01-22 Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection Papazyan, Romeo Ferdyan, Nicky Srinivasan, Karthik Gonzalez, Carlos Shannon, William D. Blount, Ken Fuchs, Bryan C. Microorganisms Article Microbiome-based therapeutics are increasingly evaluated as a strategy to reduce recurrent Clostridioides difficile infection (rCDI), with proposed mechanisms including restoration of the microbiota and microbiota-mediated functions, such as bile acid (BA) metabolism. This study reports a quantitative and sensitive assay for targeted metabolomic assessment, and the application of the assay to profile BA composition in a Phase 2 trial of the investigational microbiota-based live biotherapeutic RBX2660 for reduction of rCDI. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 35 BAs from 113 participant stool samples from 27 RBX2660-treated rCDI participants in the double-blinded, placebo-controlled clinical trial. The results demonstrate a high-confidence assay as represented by sensitivity, linearity, accuracy, and precision. Furthermore, the assay enabled the observation of primary BAs as the dominant BA species at baseline in stool samples from clinical trial participants, consistent with the expected loss of commensals after broad-spectrum antibiotic treatment. After RBX2660 administration, there was a significant drop in primary BAs concurrent with increased secondary BAs that sustained through 24 months post-RBX2660. Taken together, we describe a robust assay that demonstrates altered BA metabolism in rCDI patients treated with RBX2660 administration. MDPI 2023-01-05 /pmc/articles/PMC9865816/ /pubmed/36677428 http://dx.doi.org/10.3390/microorganisms11010135 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papazyan, Romeo
Ferdyan, Nicky
Srinivasan, Karthik
Gonzalez, Carlos
Shannon, William D.
Blount, Ken
Fuchs, Bryan C.
Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection
title Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection
title_full Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection
title_fullStr Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection
title_full_unstemmed Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection
title_short Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Clostridioides difficile Infection
title_sort human fecal bile acid analysis after investigational microbiota-based live biotherapeutic delivery for recurrent clostridioides difficile infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865816/
https://www.ncbi.nlm.nih.gov/pubmed/36677428
http://dx.doi.org/10.3390/microorganisms11010135
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