title: Maternal Antibiotic Treatment Impacts Development of the Neonatal Intestinal Microbiome and Antiviral Immunity.
abstract: Microbial colonization of the infant gastrointestinal tract (GIT) begins at birth, is shaped by the maternal microbiota, and is profoundly altered by antibiotic treatment. Antibiotic treatment of mothers during pregnancy influences colonization of the GIT microbiota of their infants. The role of the GIT microbiota in regulating adaptive immune function against systemic viral infections during infancy remains undefined. We used a mouse model of perinatal antibiotic exposure to examine the effect of GIT microbial dysbiosis on infant CD8(+) T cell-mediated antiviral immunity. Maternal antibiotic treatment/treated (MAT) during pregnancy and lactation resulted in profound alterations in the composition of the GIT microbiota in mothers and infants. Streptococcus spp. dominated the GIT microbiota of MAT mothers, whereas Enterococcus faecalis predominated within the MAT infant GIT. MAT infant mice subsequently exhibited increased and accelerated mortality following vaccinia virus infection. Ag-specific IFN-γ-producing CD8(+) T cells were reduced in sublethally infected MAT infant mice. MAT CD8(+) T cells from uninfected infant mice also demonstrated a reduced capacity to sustain IFN-γ production following in vitro activation. We additionally determined that control infant mice became more susceptible to infection if they were born in an animal facility using stricter standards of hygiene. These data indicate that undisturbed colonization and progression of the GIT microbiota during infancy are necessary to promote robust adaptive antiviral immune responses.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University, New York, NY 10032; and.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gonzalez-Perez
authors.affiliation: Center for Infection and Immunity, Columbia University, New York, NY 10032.
authors.forename: Allison L
authors.identifier: 0000-0001-9208-6371
authors.initials: AL
authors.lastname: Hicks
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University, New York, NY 10032; and.
authors.forename: Tessa M
authors.initials: TM
authors.lastname: Tekieli
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University, New York, NY 10032; and.
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Radens
authors.affiliation: Center for Infection and Immunity, Columbia University, New York, NY 10032.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Williams
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University, New York, NY 10032; and enl2118@cumc.columbia.edu.
authors.forename: Esi S N
authors.identifier: 0000-0002-1067-5795
authors.initials: ES
authors.lastname: Lamousé-Smith
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D013293:Enterococcus faecalis / Q000502:physiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D007371:Interferon-gamma / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013291:Streptococcus / Q000502:physiology*; D014615:Vaccinia / Q000276:immunology / Q000382:microbiology*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D007371:Interferon-gamma