The goal of this prospective longitudinal cohort study is to examine how the human microbiome of pregnant women-including bacteria and fungi in the gastrointestinal tract, vaginal canal, skin, and breastmilk-may influence infant gut inflammation, measured by fecal calprotectin (FCP) levels, and to identify factors that could inform dietary interventions to improve infant health outcomes. Specifically, the study aims to determine which maternal gut microbiome characteristics and dietary patterns during pregnancy are associated with elevated FCP levels in infants, and which infant gut microbiota compositions and dietary factors are linked to high FCP levels. Researchers will compare microbiome signatures and dietary factors in pregnant women and their infants with active or inactive IBD, as well as non-IBD controls, to identify microbial patterns that may predict infant gut inflammation. Participants will provide fecal samples at all study timepoints, one vaginal swab during the third trimester of pregnancy, and optional breastmilk and breast skin swab samples. They will also complete 3-day diet recalls using a smartphone app and participate in a longitudinal follow-up over 12 months after birth to monitor dietary patterns, microbiome profiles, and gut inflammation in both mother and infant.
Pregnant individuals ≥19 years recruited during their first, second or early third trimester.
Own or have regular access to a smartphone compatible with the study smartphone application RXFood.
Inability to provide consent
Previous gastrointestinal cancer or bowel surgery
Renal disease
HIV/AIDS or other serious infection
The investigators aim to have a total of 80 pregnant participants enrolled before week 35 of gestation. Patient grouping for recruitment is as follows:Group 1: 40 pregnant participants with a confirmed diagnosis of IBD, including either Crohn's Disease (CD) or Ulcerative Colitis (UC). Participants will have varying disease severity levels as determined by their gastroenterologist using standardized scoring systems: SES-CD (Simple Endoscopic Score for Crohn's Disease) for CD patients and Mayo score for UC patients.Group 2: 40 Control Pregnant individuals without a diagnosis of IBD, matched as controls for comparison.
Cohort
Prospective
Not listed
Correlation between maternal gut microbiota during pregnancy (third trimester) and early postpartum period (2 weeks, 3 months, and 1 year) and infant FCP levels at 3 months and 1 year of age, accounting for maternal adherence to Mediterranean diet.
FCP, a marker of intestinal inflammation, will be quantified in maternal stool samples collected during the third trimester of pregnancy and the early postpartum period (2 weeks, 3 months, and 1 year postpartum), as well as in infant stool samples collected at 3 months and 1 year of age, using enzyme-linked immunosorbent assay (ELISA). Elevated infant FCP is defined as \>400 µg/g. Maternal gut microbiota composition and diversity will be characterized using long-read Oxford Nanopore 16S rRNA sequencing, and microbial metabolites will be quantified using gas chromatography-mass spectrometry (GC-MS). Maternal dietary intake during the third trimester and postpartum period will be assessed using 3-day dietary records completed via the RXFood mobile application. Adherence to the Mediterranean diet will be scored using the Mediterranean Diet Score (MDS; range 0-7), with scores of 4-7 indicating high Mediterranean diet adherence.
Develop and validate a machine learning model for predicting elevated infant FCP levels at 1 year of age using maternal gut microbiota composition and dietary patterns as predictive features.
This multi-modal integrative supervised machine learning (sPLS-DA33; http://mixomics.org/) will integrate infant and pregnancy gut microbiota and dietary features to predict elevated infant FCP levels at 1 year. These features will be used to train predictive models with Random Forest Classifier and Artificial neural networks (ANN) providing complementary approaches for robust prediction. Cross-validation (20 × 5-fold) will optimize model performance and generalizability.
Characterize and compare HMO profiles between mothers with and without IBD, and determine their associations with the infant gut microbiota composition and the infant FCP levels at 3 months and 1 year of age.
Human milk oligosaccharide (HMO) composition will be characterized and compared between mothers with IBD and healthy controls using breastmilk samples collected postpartum. Participants will be asked to perform a full breast expression (\~5-10 mL) and the breastmilk will be alliquot and stored at -80 degrees freezer. Breastmilk composition, specifically HMO, will be analyzed using ultra-performance liquid chromatography with fluorescence (UPLC-FL) in Dr. Lars Bode laboratory from the University of California San Diego. The study will identify specific HMO profiles and assess their associations with infant gut microbiota composition and fecal calprotectin (FCP) levels at 3 months and 1 year of age. This analysis will help determine whether maternal IBD status could influence HMO composition and whether specific HMO profiles impact infant gut health and inflammation markers, potentially informing nutritional strategies to support optimal infant gastrointestinal development.
Compare pregnancy outcomes between mothers with ulcerative colitis or Crohn's disease and those without IBD.
Pregnancy outcomes will be collected via chart review, and via a questionnaire completed by the participant to gather data on health outcomes. This study will compare pregnancy outcomes between mothers with ulcerative colitis (UC) or Crohn's disease (CD) and those without IBD. The analysis will examine the impact of IBD therapies, including steroids and advanced biologics, on maternal and infant health outcomes. Additionally, the study will investigate the relationship between mode of delivery (vaginal versus cesarean section) and outcomes for both mothers and infants. This comparison will provide insights into how IBD disease management and delivery methods influence pregnancy-related health outcomes, contributing to evidence-based care recommendations for pregnant individuals with IBD.
Correlation between maternal dietary patterns (macro and micronutrients) and maternal microbiota composition (gut, skin, and vaginal) and maternal and infant clinical outcomes, including pregnancy and postpartum complications.
Maternal dietary patterns will be assessed using 3-day food diaries collected via RxFood, an AI-enabled dietary assessment application. Maternal microbiota composition (gut, breast skin, and vaginal) will be analyzed in relation to pregnancy and postpartum complications assessed during the third trimester and at 2 weeks, 3 months, and 1 year postpartum. Infant clinical outcomes will be assessed at birth, 2 weeks, 3 months, and 1 year of age using participant-completed questionnaires and review of relevant medical records.
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University of British Columbia
Lead sponsor
BC Children's Hospital Research Institute
Collaborator
IBD Centre of BC
Collaborator
