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

Laurent Ferraris , Aurélie Balvay , Deborah Bellet (1) , Johanne Delannoy , Claire Maudet (1) , Thibaut Larcher (2) , Jean-Christophe Rozé (3) , Catherine Philippe (1) , Thierry Meylheuc (1) , Marie-José Butel , Sylvie Rabot (1) , Julio Aires

1 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
2 PAnTher - Physiopathologie Animale et bioThérapie du muscle et du système nerveux
3 PhAN - Physiopathologie des Adaptations Nutritionnelles

Bacterial 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.

Mots clés: Clostridium butyricum; Clostridium neonatale; necrotizing enterocolitis; butyrate; animal model; beta-hydroxybutyryl-CoA dehydrogenase; NEC; NEClike lesions; NEC-like lesions

Domaines: Sciences du Vivant [q-bio]

Laurent Ferraris, Aurélie Balvay, Deborah Bellet, Johanne Delannoy, Claire Maudet, et al.. Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity. Gut microbes, 2023, 15 (1), pp.2172666. ⟨10.1080/19490976.2023.2172666⟩. ⟨hal-04106612⟩