# Effect of Maternal IBD, Microbiome and Early Life Events on the Bacterial Colonization and Mucosal Immunity in the Offspring

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $211,250

## Abstract

SUMMARY
Inflammatory bowel disease (IBD) is a chronic condition of the gastrointestinal tract that is caused by the loss
of mucosal tolerance towards the commensal microbiota resulting in chronic inflammation. Importantly, IBD
affects women during their reproductive years and 25% become pregnant after their initial diagnosis. The
bacterial composition in the gut, or microbiome, has emerged as an important determinant of IBD
pathogenesis. Moreover, increasing evidence suggests that early life exposures may modulate the risk of IBD
later in life and that maternal health and microbiota composition during pregnancy may influence the baby’s gut
colonization and play an essential role in shaping the immune system. We demonstrated that pregnant women
with IBD and their babies have a significantly less diverse and more pro-inflammatory microbiota compared to
no-IBD controls, and that the microbiome of 3-month old babies born to IBD mothers, when inoculated into
germ-free mice, triggers the development of an imbalanced immune system. Yet, it remains largely unknown
how maternal IBD and other early life events affect the offspring’s microbiome assembly and mucosal
immunity. Therefore, the objectives of this proposal are to 1) track particular bacterial strains originated from or
informed by the maternal gut microbiota, bacterial metabolites in the umbilical cord blood, and inflammatory
proteins in the breast milk that colonize the gut of babies born to mothers with and without IBD; 2) determine
how maternal IBD and other early life events can modify the priming of the initial microbiome and mucosal
immunity, and 3) validate if bacterial strains or metabolites enriched in babies born to mothers with IBD are
detected in high IBD risk first degree relatives prior to IBD diagnosis using two independent cohorts. We will
expand on the ongoing MECONIUM (MEChanisms Of disease traNsmission In Utero through the Microbiome)
study that follows 430 pregnant women with and without IBD and their babies with >5,500 samples collected.
We will use extensive data, including 16S rRNA gene sequencing during pregnancy and in babies at numerous
time points over the first 3 years of life, metagenomic data on mother-baby pairs, cord blood metabolomics,
and breast milk proteomics, coupled with health status, clinical information, medications, mode of delivery,
feeding behavior, etc., to identify the sources and predictors of the early microbiome colonization. Next, given
that fecal calprotectin is a significant predictor of IBD incidence in high risk individuals, we will characterize the
degree of mucosal inflammation, assessed by fecal calprotectin, in babies born to mothers with and without
IBD. This multifaceted study will shed new light on the origin and maturation of the early life microbiome in the
setting of maternal health and disease during the most sensitive time for the priming of the immune system.
Study findings, validated in two independent prospective cohorts, can he...

## Key facts

- **NIH application ID:** 10469405
- **Project number:** 5R21DK125906-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jose C Clemente
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $211,250
- **Award type:** 5
- **Project period:** 2021-08-13 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469405

## Citation

> US National Institutes of Health, RePORTER application 10469405, Effect of Maternal IBD, Microbiome and Early Life Events on the Bacterial Colonization and Mucosal Immunity in the Offspring (5R21DK125906-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469405. Licensed CC0.

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