Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly

ABSTRACT A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sudeep Ghimire, Chayan Roy, Supapit Wongkuna, Linto Antony, Abhijit Maji, Mitchel Chan Keena, Andrew Foley, Joy Scaria
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Clostridium difficile coculture colonization resistance culturomics fatty acids metagenomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5c2f86ce500f4fbe802168f6b8c0e1cf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5c2f86ce500f4fbe802168f6b8c0e1cf
record_format	dspace
spelling	oai:doaj.org-article:5c2f86ce500f4fbe802168f6b8c0e1cf2021-12-02T19:46:20ZIdentification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly10.1128/mSystems.00620-192379-5077https://doaj.org/article/5c2f86ce500f4fbe802168f6b8c0e1cf2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00620-19https://doaj.org/toc/2379-5077ABSTRACT A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1,590 isolates belonging to 102 species. This culture collection represents 34.57% of the taxonomic diversity and 70% functional capacity, as estimated by metagenomic sequencing of the fecal samples used for culture. Using whole-genome sequencing, we characterized species representatives from this collection and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profiles and short-chain fatty acid production. When screened with a coculture assay, 66 species in our culture collection inhibited Clostridioides difficile. Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol, or succinate, correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile. We tested 256 combinations and found that both species composition and blend size were important in inhibition. Our results show that the interaction of bacteria with one another in a mix and with other members of gut commensals must be investigated to design defined bacterial mixes for inhibiting C. difficile in vivo. IMPORTANCE Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile-inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.Sudeep GhimireChayan RoySupapit WongkunaLinto AntonyAbhijit MajiMitchel Chan KeenaAndrew FoleyJoy ScariaAmerican Society for MicrobiologyarticleClostridium difficilecoculturecolonization resistanceculturomicsfatty acidsmetagenomicsMicrobiologyQR1-502ENmSystems, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridium difficile coculture colonization resistance culturomics fatty acids metagenomics Microbiology QR1-502
spellingShingle	Clostridium difficile coculture colonization resistance culturomics fatty acids metagenomics Microbiology QR1-502 Sudeep Ghimire Chayan Roy Supapit Wongkuna Linto Antony Abhijit Maji Mitchel Chan Keena Andrew Foley Joy Scaria Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly
description	ABSTRACT A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1,590 isolates belonging to 102 species. This culture collection represents 34.57% of the taxonomic diversity and 70% functional capacity, as estimated by metagenomic sequencing of the fecal samples used for culture. Using whole-genome sequencing, we characterized species representatives from this collection and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profiles and short-chain fatty acid production. When screened with a coculture assay, 66 species in our culture collection inhibited Clostridioides difficile. Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol, or succinate, correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile. We tested 256 combinations and found that both species composition and blend size were important in inhibition. Our results show that the interaction of bacteria with one another in a mix and with other members of gut commensals must be investigated to design defined bacterial mixes for inhibiting C. difficile in vivo. IMPORTANCE Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile-inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.
format	article
author	Sudeep Ghimire Chayan Roy Supapit Wongkuna Linto Antony Abhijit Maji Mitchel Chan Keena Andrew Foley Joy Scaria
author_facet	Sudeep Ghimire Chayan Roy Supapit Wongkuna Linto Antony Abhijit Maji Mitchel Chan Keena Andrew Foley Joy Scaria
author_sort	Sudeep Ghimire
title	Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly
title_short	Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly
title_full	Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly
title_fullStr	Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly
title_full_unstemmed	Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly
title_sort	identification of <named-content content-type="genus-species">clostridioides difficile</named-content>-inhibiting gut commensals using culturomics, phenotyping, and combinatorial community assembly
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/5c2f86ce500f4fbe802168f6b8c0e1cf
work_keys_str_mv	AT sudeepghimire identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT chayanroy identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT supapitwongkuna identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT lintoantony identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT abhijitmaji identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT mitchelchankeena identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT andrewfoley identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly AT joyscaria identificationofnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinhibitinggutcommensalsusingculturomicsphenotypingandcombinatorialcommunityassembly
_version_	1718375963206615040

Identification of <named-content content-type="genus-species">Clostridioides difficile</named-content>-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly

Ejemplares similares