Elevated Fecal Lipocalin-2 Levels During Early Life Are Associated with Maternal Inflammatory Bowel Disease Diagnosis

Fecal lipocalin-2 (LCN2) is a biomarker of neutrophil activation, which is elevated in patients with inflammatory bowel disease (IBD); however, its dynamic changes during pregnancy and early life are largely unknown. We characterized LCN2 levels by maternal IBD diagnosis, offspring feeding behavior, and gut microbiota composition.

In the prospective MECONIUM (Exploring Mechanisms of Disease Transmission In Utero through the Microbiome) study, we analyzed 559 fecal samples from 91 pregnant women with IBD, 78 healthy controls, and their 147 offspring for LCN2 levels at each trimester of pregnancy and multiple time points during early life using linear mixed-effects model and multiple logistic regression analyses. Gut microbiota community compositions were evaluated following 16S rRNA gene sequencing.

IBD cases had higher LCN2 levels throughout pregnancy compared to controls. In offspring, significantly higher LCN2 was found in babies born to mothers with IBD, compared to those without IBD, at 3 months, 1 year, and 4 years (all p < 0.03), with offspring LCN2 levels being predictive of maternal IBD case status with > 85% accuracy at ages 1 and 4. We also detected correlations between LCN2 levels and certain IBD-associated bacterial taxa in both mothers and babies. Exclusively breastfed babies had lower LCN2 in the first weeks of life compared to formula or mixed-fed counterparts.

Babies born to mother with IBD had significantly higher LCN2 during early life compared to controls with exclusive breastfeeding impacting LCN2 levels early on. LCN2 levels correlated with IBD-associated microbial taxa in both mothers and babies. Future studies should identify the biological drivers and health-related consequences of elevated LCN2 during early childhood.