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- Title
Antibiotic use during pregnancy is linked to offspring gut microbial dysbiosis, barrier disruption, and altered immunity along the gut–lung axis.
- Authors
Alhasan, Moumen M.; Hölsken, Oliver; Duerr, Claudia; Helfrich, Sofia; Branzk, Nora; Philipp, Alina; Leitz, Dominik; Duerr, Julia; Almousa, Yahia; Barrientos, Gabriela; Mohn, William W.; Gamradt, Stefanie; Conrad, Melanie L.
- Abstract
Antibiotic use during pregnancy is associated with increased asthma risk in children. Since approximately 25% of women use antibiotics during pregnancy, it is important to identify the pathways involved in this phenomenon. We investigate how mother‐to‐offspring transfer of antibiotic‐induced gut microbial dysbiosis influences immune system development along the gut–lung axis. Using a mouse model of maternal antibiotic exposure during pregnancy, we immunophenotyped offspring in early life and after asthma induction. In early life, prenatal‐antibiotic exposed offspring exhibited gut microbial dysbiosis, intestinal inflammation (increased fecal lipocalin‐2 and IgA), and dysregulated intestinal ILC3 subtypes. Intestinal barrier dysfunction in the offspring was indicated by a FITC‐dextran intestinal permeability assay and circulating lipopolysaccharide. This was accompanied by increased T‐helper (Th)17 cell percentages in the offspring's blood and lungs in both early life and after allergy induction. Lung tissue additionally showed increased percentages of RORγt T‐regulatory (Treg) cells at both time points. Our investigation of the gut–lung axis identifies early‐life gut dysbiosis, intestinal inflammation, and barrier dysfunction as a possible developmental programming event promoting increased expression of RORγt in blood and lung CD4+ T cells that may contribute to increased asthma risk.
- Subjects
DYSBIOSIS; ASTHMA in children; PREGNANCY; T cells; MATERNAL exposure
- Publication
European Journal of Immunology, 2023, Vol 53, Issue 10, p1
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.202350394