Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures

ABSTRACT Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may...

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Autores principales:	Regina Lamendella, Justin R. Wright, Jada Hackman, Christopher McLimans, David R. Toole, William Bernard Rubio, Rebecca Drucker, Hoi Tong Wong, Kate Sabey, John P. Hegarty, David B. Stewart
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Clostridium difficile infection antibiotic treatments intestinal dysbiosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/79863b9b8ce4472dae590952fc485231
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spelling	oai:doaj.org-article:79863b9b8ce4472dae590952fc4852312021-11-15T15:22:01ZAntibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures10.1128/mSphere.00572-172379-5042https://doaj.org/article/79863b9b8ce4472dae590952fc4852312018-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00572-17https://doaj.org/toc/2379-5042ABSTRACT Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were either not antibiotic treated or treated with metronidazole, vancomycin, or fidaxomicin, the three most common CDI therapies. The microbial community composition, interactions, and predicted metabolic functions were assessed by 16S rRNA gene and internal transcribed spacer sequencing, bipartite network analysis, and phylogenetic investigation of communities by reconstruction of unobserved states. Our results demonstrate that while all C. difficile-directed antibiotics were associated with similar reductions in alpha diversity, beta diversity significantly differed on the basis of the particular antibiotic, with differentiating relative abundances of bacterial and fungal assemblages. With the exception of fidaxomicin, each antibiotic was associated with the emergence of potentially pathogenic fungal operational taxonomic units, with predicted bacterial functions enriched for xenobiotic metabolism that could perpetuate the dysbiosis driving CDI. Toxin-independent mechanisms of colitis related to the relative abundance of pathogenic bacteria and fungi were also noted. This study suggests that a transkingdom interaction between fungi and bacteria may be important in CDI pathophysiology, including being a factor in the historically high persistence and recurrence rates associated with this disease. IMPORTANCE Using human fecal samples and including sequencing for both bacterial and fungal taxa, this study compared the conventional antibiotics used to treat C. difficile infection (CDI) from the perspective of the microbiome, which is particularly relevant, given the relationship between dysbiotic states and the development of CDI. Sequencing and imputed functional analyses suggest that C. difficile-directed antibiotics are associated with distinct forms of dysbiosis that may be influential in the course of CDI. Further, a role for fungal organisms in the perpetuation of the causal dysbiosis of CDI is discussed, suggesting a previously unappreciated, clinically relevant transkingdom interaction that warrants further study.Regina LamendellaJustin R. WrightJada HackmanChristopher McLimansDavid R. TooleWilliam Bernard RubioRebecca DruckerHoi Tong WongKate SabeyJohn P. HegartyDavid B. StewartAmerican Society for MicrobiologyarticleClostridium difficile infectionantibiotic treatmentsintestinal dysbiosisMicrobiologyQR1-502ENmSphere, Vol 3, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridium difficile infection antibiotic treatments intestinal dysbiosis Microbiology QR1-502
spellingShingle	Clostridium difficile infection antibiotic treatments intestinal dysbiosis Microbiology QR1-502 Regina Lamendella Justin R. Wright Jada Hackman Christopher McLimans David R. Toole William Bernard Rubio Rebecca Drucker Hoi Tong Wong Kate Sabey John P. Hegarty David B. Stewart Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures
description	ABSTRACT Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were either not antibiotic treated or treated with metronidazole, vancomycin, or fidaxomicin, the three most common CDI therapies. The microbial community composition, interactions, and predicted metabolic functions were assessed by 16S rRNA gene and internal transcribed spacer sequencing, bipartite network analysis, and phylogenetic investigation of communities by reconstruction of unobserved states. Our results demonstrate that while all C. difficile-directed antibiotics were associated with similar reductions in alpha diversity, beta diversity significantly differed on the basis of the particular antibiotic, with differentiating relative abundances of bacterial and fungal assemblages. With the exception of fidaxomicin, each antibiotic was associated with the emergence of potentially pathogenic fungal operational taxonomic units, with predicted bacterial functions enriched for xenobiotic metabolism that could perpetuate the dysbiosis driving CDI. Toxin-independent mechanisms of colitis related to the relative abundance of pathogenic bacteria and fungi were also noted. This study suggests that a transkingdom interaction between fungi and bacteria may be important in CDI pathophysiology, including being a factor in the historically high persistence and recurrence rates associated with this disease. IMPORTANCE Using human fecal samples and including sequencing for both bacterial and fungal taxa, this study compared the conventional antibiotics used to treat C. difficile infection (CDI) from the perspective of the microbiome, which is particularly relevant, given the relationship between dysbiotic states and the development of CDI. Sequencing and imputed functional analyses suggest that C. difficile-directed antibiotics are associated with distinct forms of dysbiosis that may be influential in the course of CDI. Further, a role for fungal organisms in the perpetuation of the causal dysbiosis of CDI is discussed, suggesting a previously unappreciated, clinically relevant transkingdom interaction that warrants further study.
format	article
author	Regina Lamendella Justin R. Wright Jada Hackman Christopher McLimans David R. Toole William Bernard Rubio Rebecca Drucker Hoi Tong Wong Kate Sabey John P. Hegarty David B. Stewart
author_facet	Regina Lamendella Justin R. Wright Jada Hackman Christopher McLimans David R. Toole William Bernard Rubio Rebecca Drucker Hoi Tong Wong Kate Sabey John P. Hegarty David B. Stewart
author_sort	Regina Lamendella
title	Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures
title_short	Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures
title_full	Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures
title_fullStr	Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures
title_full_unstemmed	Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures
title_sort	antibiotic treatments for <named-content content-type="genus-species">clostridium difficile</named-content> infection are associated with distinct bacterial and fungal community structures
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/79863b9b8ce4472dae590952fc485231
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Antibiotic Treatments for <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Are Associated with Distinct Bacterial and Fungal Community Structures

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