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Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota

BACKGROUND AND AIMS: Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) thera...

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Autores principales: Munyaka, Peris Mumbi, Eissa, N., Bernstein, Charles Noah, Khafipour, Ehsan, Ghia, Jean-Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659638/
https://www.ncbi.nlm.nih.gov/pubmed/26605545
http://dx.doi.org/10.1371/journal.pone.0142536
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author Munyaka, Peris Mumbi
Eissa, N.
Bernstein, Charles Noah
Khafipour, Ehsan
Ghia, Jean-Eric
author_facet Munyaka, Peris Mumbi
Eissa, N.
Bernstein, Charles Noah
Khafipour, Ehsan
Ghia, Jean-Eric
author_sort Munyaka, Peris Mumbi
collection PubMed
description BACKGROUND AND AIMS: Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. METHODS: Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. RESULTS: ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. CONCLUSIONS: The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.
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spelling pubmed-46596382015-12-02 Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota Munyaka, Peris Mumbi Eissa, N. Bernstein, Charles Noah Khafipour, Ehsan Ghia, Jean-Eric PLoS One Research Article BACKGROUND AND AIMS: Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. METHODS: Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. RESULTS: ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. CONCLUSIONS: The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers. Public Library of Science 2015-11-25 /pmc/articles/PMC4659638/ /pubmed/26605545 http://dx.doi.org/10.1371/journal.pone.0142536 Text en © 2015 Munyaka et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Munyaka, Peris Mumbi
Eissa, N.
Bernstein, Charles Noah
Khafipour, Ehsan
Ghia, Jean-Eric
Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota
title Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota
title_full Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota
title_fullStr Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota
title_full_unstemmed Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota
title_short Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota
title_sort antepartum antibiotic treatment increases offspring susceptibility to experimental colitis: a role of the gut microbiota
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659638/
https://www.ncbi.nlm.nih.gov/pubmed/26605545
http://dx.doi.org/10.1371/journal.pone.0142536
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