Antibiotic use during pregnancy is linked to offspring gut microbial dysbiosis, barrier disruption, and altered immunity along the gut–lung axis

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.

Nutrition during pregnancy: Influence on the gut microbiome and fetal development

“…Now, decades later, both epidemiological observations and proof‐of‐concept animal models have demonstrated the substantial effect that the early‐life environment has on fetal and neonatal development 3,4 . In addition to nutrition, many studies have identified other environmental influences during pregnancy that play a major role in offspring development and overall health including (but not exhaustive): antibiotic use during pregnancy, 5–7 maternal immune activation, 8–10 stress, 11,12 and vaginal microbiome exposure 13 . This research has provided a framework for the Developmental Origins of Health and Disease Hypothesis (DOHaD), 3,14,15 which states that environmental cues present during critical perinatal time points developmentally program offspring organ systems and subsequently influence individual health outcomes.…”