Peer-reviewed article
Maternal-Fetal Exposome and Early-Life Microbiota-Pattern Recognition Receptors Signaling in Inflammatory Bowel Disease Susceptibility: A Mechanistic Review.
Jurkiewicz K, Smolinska-Wilczynska S ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a mechanistic review of how prenatal and early-life exposures may influence susceptibility to inflammatory bowel disease in children. It synthesizes findings from human studies, animal models, and cellular research to examine interactions between maternal factors, microbiota, environmental exposures, and immune development. The review proposes a theoretical model of how microbial sensing during early life might promote either immune tolerance or inflammatory readiness, but notes this model remains unproven in humans.
Key points
- Early-life antibiotic use shows the strongest association with later IBD in human cohort studies
- Maternal microbial signals and immune features are altered in pregnancies affected by IBD, but causality is not established
- Experimental models demonstrate that microbial metabolites regulate immune cells and barrier function in offspring
- A proposed 'developmental inflammatory set-point' model suggests timing, signal intensity, and host genotype determine whether microbial sensing promotes tolerance or inflammatory readiness
- The model is biologically plausible but remains unvalidated as a predictor of human IBD
Limitations
This is a narrative review synthesizing existing literature rather than original research, so it cannot establish causality for any associations. The evidence base is heterogeneous, with human observational studies vulnerable to confounding, and the proposed theoretical model remains unproven in human populations.
Abstract
Inflammatory bowel disease (IBD) develops through interactions among genetic susceptibility, intestinal microbiota, environmental exposures, and dysregulated mucosal immunity. Increasing evidence suggests that these interactions may begin before diagnosis-and possibly before birth-when maternal signals, microbial assembly, epithelial maturation, and immune education intersect. This narrative review synthesizes findings from human observational and cohort studies, experimental animal and cellular models, and mechanistic literature to examine how prenatal and early-life exposures may influence later IBD susceptibility. Human cohort studies associate later IBD with several early-life exposures, particularly repeated antibiotic use, whereas evidence for dietary, delivery, and household factors remains heterogeneous and vulnerable to confounding. Studies of pregnancies affected by IBD identify altered maternal and infant microbial and immune features but do not establish causality. Experimental models provide stronger mechanistic evidence that maternal microbial signals influence offspring immune development, neonatal epithelial cells acquire context-dependent tolerance, and microbial metabolites regulate regulatory T cells, type 17 immunity, barrier function, and chromatin-modifying enzymes. Histamine-receptor signaling further illustrates receptor-specific modulation of bacterial TLR (Toll-like receptors) responses in established IBD, although its role in early-life programming remains unproven. We propose a testable "developmental inflammatory set-point" model in which cell type, tissue compartment, timing, signal intensity, and host genotype determine whether microbial sensing promotes tolerance or persistent inflammatory readiness. This model is biologically plausible but remains unvalidated as a predictor of human IBD.