Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity

ABSTRACTBacterial colonization in the gut plays a pivotal role in neonatal necrotizing enterocolitis (NEC) development, but the relationship between bacteria and NEC remains unclear. In this study, we aimed to elucidate whether bacterial butyrate end-fermentation metabolites participate in the devel...

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Main Authors: Laurent Ferraris, Aurélie Balvay, Deborah Bellet, Johanne Delannoy, Claire Maudet, Thibaut Larcher, Jean-Christophe Rozé, Catherine Philippe, Thierry Meylheuc, Marie-José Butel, Sylvie Rabot, Julio Aires
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2023.2172666
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author Laurent Ferraris
Aurélie Balvay
Deborah Bellet
Johanne Delannoy
Claire Maudet
Thibaut Larcher
Jean-Christophe Rozé
Catherine Philippe
Thierry Meylheuc
Marie-José Butel
Sylvie Rabot
Julio Aires
author_facet Laurent Ferraris
Aurélie Balvay
Deborah Bellet
Johanne Delannoy
Claire Maudet
Thibaut Larcher
Jean-Christophe Rozé
Catherine Philippe
Thierry Meylheuc
Marie-José Butel
Sylvie Rabot
Julio Aires
author_sort Laurent Ferraris
collection DOAJ
description ABSTRACTBacterial colonization in the gut plays a pivotal role in neonatal necrotizing enterocolitis (NEC) development, but the relationship between bacteria and NEC remains unclear. In this study, we aimed to elucidate whether bacterial butyrate end-fermentation metabolites participate in the development of NEC lesions and confirm the enteropathogenicity of Clostridium butyricum and Clostridium neonatale in NEC. First, we produced C.butyricum and C.neonatale strains impaired in butyrate production by genetically inactivating the hbd gene encoding β-hydroxybutyryl-CoA dehydrogenase that produces end-fermentation metabolites. Second, we evaluated the enteropathogenicty of the hbd-knockout strains in a gnotobiotic quail model of NEC. The analyses showed that animals harboring these strains had significantly fewer and less intense intestinal lesions than those harboring the respective wild-type strains. In the absence of specific biological markers of NEC, the data provide original and new mechanistic insights into the disease pathophysiology, a necessary step for developing potential novel therapies.
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spelling doaj.art-f6c8c34fe93248af80243bd2a99231722024-03-28T22:38:19ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2023.2172666Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicityLaurent Ferraris0Aurélie Balvay1Deborah Bellet2Johanne Delannoy3Claire Maudet4Thibaut Larcher5Jean-Christophe Rozé6Catherine Philippe7Thierry Meylheuc8Marie-José Butel9Sylvie Rabot10Julio Aires11Université Paris Cité, INSERM, UMR-S 1139, 3PHM, Paris, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris Cité, INSERM, UMR-S 1139, 3PHM, Paris, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceINRAE, Oniris, PAnTher, APEX, Nantes, FranceINRAE, UMR 1280, Physiologie des Adaptations Nutritionnelles (PhAN), Université hospitalière de Nantes, Nantes, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris Cité, INSERM, UMR-S 1139, 3PHM, Paris, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceUniversité Paris Cité, INSERM, UMR-S 1139, 3PHM, Paris, FranceABSTRACTBacterial colonization in the gut plays a pivotal role in neonatal necrotizing enterocolitis (NEC) development, but the relationship between bacteria and NEC remains unclear. In this study, we aimed to elucidate whether bacterial butyrate end-fermentation metabolites participate in the development of NEC lesions and confirm the enteropathogenicity of Clostridium butyricum and Clostridium neonatale in NEC. First, we produced C.butyricum and C.neonatale strains impaired in butyrate production by genetically inactivating the hbd gene encoding β-hydroxybutyryl-CoA dehydrogenase that produces end-fermentation metabolites. Second, we evaluated the enteropathogenicty of the hbd-knockout strains in a gnotobiotic quail model of NEC. The analyses showed that animals harboring these strains had significantly fewer and less intense intestinal lesions than those harboring the respective wild-type strains. In the absence of specific biological markers of NEC, the data provide original and new mechanistic insights into the disease pathophysiology, a necessary step for developing potential novel therapies.https://www.tandfonline.com/doi/10.1080/19490976.2023.2172666Clostridium butyricumClostridium neonatalenecrotizing enterocolitisbutyrateanimal modelbeta-hydroxybutyryl-CoA dehydrogenase
spellingShingle Laurent Ferraris
Aurélie Balvay
Deborah Bellet
Johanne Delannoy
Claire Maudet
Thibaut Larcher
Jean-Christophe Rozé
Catherine Philippe
Thierry Meylheuc
Marie-José Butel
Sylvie Rabot
Julio Aires
Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity
Gut Microbes
Clostridium butyricum
Clostridium neonatale
necrotizing enterocolitis
butyrate
animal model
beta-hydroxybutyryl-CoA dehydrogenase
title Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity
title_full Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity
title_fullStr Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity
title_full_unstemmed Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity
title_short Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity
title_sort neonatal necrotizing enterocolitis clostridium butyricum and clostridium neonatale fermentation metabolism and enteropathogenicity
topic Clostridium butyricum
Clostridium neonatale
necrotizing enterocolitis
butyrate
animal model
beta-hydroxybutyryl-CoA dehydrogenase
url https://www.tandfonline.com/doi/10.1080/19490976.2023.2172666
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