Influence of Early Life Factors, including Breastmilk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Herein we analyzed the influence of early life factors, including breastmilk composition on the development of the intestinal microbiota of infants born to mothers with and without IBD.

METHODS: The MECONIUM (Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome) study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analyzed using 16s rRNA sequencing and fecal calprotectin. Breastmilk proteomics was profiled using Olink inflammation panel.

RESULTS: We analyzed gut microbiota of 1,034 fecal samples from 294 infants (80 born to mothers with and 214 to mothers without IBD). Alpha-diversity was driven by maternal IBD status and timepoint. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breastmilk samples (91 from mothers with IBD), mothers with IBD displayed lower abundance of proteins involved in immune regulation such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumor necrosis factor-beta, and C-C motif chemokine 20, as compared to control mothers (adjusted p=0.0016, 0.049, 0.049, and 0.049, respectively), with negative correlations with baby´s calprotectin, and microbiome at different time points.

CONCLUSION: Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breastmilk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and fecal calprotectin.