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Cited by 151Infant Nutrition and HealthClostridium difficile and Clostridium perfringens researchGut microbiota and health

Clostridium butyricum Strains and Dysbiosis Linked to Necrotizing Enterocolitis in Preterm Neonates

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Cassir, Nadim, Benamar, Samia, Khalil, Jacques Bou, Croce, Olivier, Saint-Faust, Marie, Jacquot, Aurélien, Million, Matthieu, Azza, Said +15 more·2015·Clinical Infectious Diseases
DOI 10.1093/cid/civ468
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Abstract

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common and serious gastrointestinal disorder among preterm neonates. We aimed to assess a specific gut microbiota profile associated with NEC. METHODS: Stool samples and clinical data were collected from 4 geographically independent neonatal intensive care units, over a 48-month period. Thirty stool samples from preterm neonates with NEC (n = 15) and controls (n = 15) were analyzed by 16S ribosomal RNA pyrosequencing and culture-based methods. The results led us to develop a specific quantitative polymerase chain reaction (qPCR) assay for Clostridium butyricum, and we tested stool samples from preterm neonates with NEC (n = 93) and controls (n = 270). We sequenced the whole genome of 16 C. butyricum strains, analyzed their phylogenetic relatedness, tested their culture supernatants for cytotoxic activity, and searched for secreted toxins. RESULTS: Clostridium butyricum was specifically associated with NEC using molecular and culture-based methods (15/15 vs 2/15; P < .0001) or qPCR (odds ratio, 45.4 [95% confidence interval, 26.2-78.6]; P < .0001). Culture supernatants of C. butyricum strains from preterm neonates with NEC (n = 14) exhibited significant cytotoxic activity (P = .008), and we identified in all a homologue of the β-hemolysin toxin gene shared by Brachyspira hyodysenteriae, the etiologic agent of swine dysentery. The corresponding protein was secreted by a NEC-associated C. butyricum strain. CONCLUSIONS: NEC was associated with C. butyricum strains and dysbiosis with an oxidized, acid, and poorly diversified gut microbiota. Our findings highlight the plausible toxigenic mechanism involved in the pathogenesis of NEC.

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  • In domestic or captive animal environments and in humans, the initiation of dysbiosis leading to domination by anaerobic clostridia, particularly by Clostridioides difficile, has been linked to antibiotic treatments, hospitalization, and neonatal microbiomes.

    “In domestic or captive animal environments and in humans, the initiation of dysbiosis leading to domination by anaerobic clostridia, particularly by Clostridioides difficile, has been linked to antibiotic treatments, hospitalization, and neonatal microbiomes (Antharam et al., 2013;Cassir et al., 2015;Popoff, 2018).”

    From Novel Lethal Clostridial Infection in Florida Manatees (Trichechus manatus latirostris): Cause of the 2013 Unusual Mortality Event in the Indian River Lagoon (2022) · cites this paper as Cassir et al., 2015

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Authors
Cassir, N., Benamar, S., Khalil, J. B., Croce, O., Saint-Faust, M., Jacquot, A., Million, M., Azza, S., Armstrong, N., Henry, M., Jardot, P., Robert, C., Gire, C., Lagier, J.-C., Chabrière, E., Ghigo, E., Marchandin, H., Sartor, C., Boutte, P., Cambonie, G., Simeoni, U., Raoult, D., & La Scola, B.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Centre Hospitalier Universitaire de Nice (FR)
  • Centre Hospitalier Universitaire de Montpellier (FR)
  • Aix-Marseille Université (FR)
  • Hôpital de la Conception (FR)
Corresponding author
Cassir, Nadim
ORCID
Venue
Clinical Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2015-06-17
Volume
61
Issue
7
Pages
1107-1115
ISSN
  • 1058-4838 (ISSN-L)
  • 1537-6591
DOI
10.1093/cid/civ468
OpenAlex
W2130581051
Cited by
151
References
2
Citations by year
2026: 4 · 2025: 9 · 2024: 15 · 2023: 16 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 15 · 2016: 22 · 2015: 3
FWCI
17.67
Type
journal article
Language
en
Open access
Locations
  • Clinical Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • HighWire Press Open Archive (submittedVersion)
Funders
Programme Hospitalier de Recherche Clinique 2009
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
Clostridium butyricum, necrotizing enterocolitis, preterm infants, gut dysbiosis, gut microbiota, cytotoxicity, toxin secretion, NEC pathogenesis, qPCR detection assay
MeSH terms
Cell Survival, Feces, France, Humans, Infant, Newborn, Infant, Premature, Cohort Studies, Jurkat Cells, Enterocolitis, Necrotizing, Clostridium butyricum, Dysbiosis

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