Abstract Background The microbiota plays an important role in the pathogenesis of Crohn’s disease and ulcerative colitis, the two major forms of inflammatory bowel diseases (IBD). Prenatal and postnatal factors such as perinatal antibiotics, mode of delivery, breast versus formula feeding, impact on microbiome development 1. The immune protein lipocalin-2 (LCN2) has been involved in innate immunity and host-microbe interaction yet was also implicated in pregnancy and early childhood events 2. Herein, we assessed the impact of maternal gut inflammation on breast milk delivery of LCN2. We assessed potential effects on microbial postnatal microbiome development in children from IBD and non-IBD mothers. Methods We followed up expectant IBD mothers and healthy pregnant controls from third trimester onwards to birth and then alongside with their offspring up one year after delivery. The project was executed as a nation-wide multicenter study. We assessed the impact of maternal gut inflammation on luminal and breast milk LCN2 levels. Further, luminal LCN2 levels and postnatal microbiome development in the offspring was studied. LCN2 content was tested by ELISA. Intestinal microbiota compositions were analysed by 16S rRNA gene sequencing 3. Microbial alpha diversity was calculated by Chao1, Shannon and Simpson indices. Beta diversity was analysed by Bray-Curtis dissimilarity. Additional analyses will utilize untargeted metabolomics to search for underlying and targetable mechanisms. Results Fecal LCN2 concentrations were highest in active compared to remittent IBD patients and healthy controls. “IBD babies” demonstrated elevated fecal LCN2 concentrations, increasing during the first three months. There was a trend to higher levels when the mother was more active. Concentrations of LCN2 in breast milk did not differ between groups yet were strongly elevated after birth and decreased gradually overtime. Noteworthy, a postpartal decline of serum LCN2 levels was observed in all mothers, IBD and non-IBD. The alpha diversity of mothers with IBD in remission was more similar to mothers with active IBD than to healthy controls, corresponding to fecal LCN2 dynamics. Infant bacterial diversities increased in a comparable manner over the first year. Conclusion Taken together, our study suggests that active disease in IBD mothers results in elevated maternal fecal LCN2 concentrations, which is reflected by increased luminal LCN2 concentration in their offspring. Effects and correlations of these findings on postpartal microbiome development based on 16S metagenomics are on the way. Furthermore, we expect that maternal inflammation will have various effects on breast milk composition which will be addressed in future studies. References: 1Hill CJ, Lynch DB, Murphy K, et al. Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome. 2017;5(1):4. Published 2017 Jan 17. doi:10.1186/s40168-016-0213-y 2Tarassishin L, Kim T, Hu J, et al. Elevated Fecal Lipocalin-2 Levels During Early Life Are Associated with Maternal Inflammatory Bowel Disease Diagnosis. Dig Dis Sci. 2025;70(3):1150-1159. doi:10.1007/s10620-025-08864-9 3Pjevac P, Hausmann B, Schwarz J, et al. An Economical and Flexible Dual Barcoding, Two-Step PCR Approach for Highly Multiplexed Amplicon Sequencing. Front Microbiol. 2021;12:669776. Published 2021 May 20. doi:10.3389/fmicb.2021.669776 Conflict of interest: Dr. Prommer, Regina: No conflict of interest Watschinger, Christina: No conflict of interest Hoog, Anna: No conflict of interest Koch, Robert: No conflict of interest Högenauer, Christoph: No conflict of interest Heeren, Sonja: No conflict of interest Megymorecz, Simone: No conflict of interest Steidl, Karin: No conflict of interest Dinkhauser, Patrick: No conflict of interest Platzer, Reingard: No conflict of interest Moschen, Alexander R.: No conflict of interest
Prommer et al. (Thu,) studied this question.