Early-life Risk Factors for Inflammatory Bowel Disease

This project will evaluate early-life risk factors associated with inflammatory bowel diseases (IBD), biomarker of
intestinal inflammation and loss of gut microbiome diversity. Candidate: The primary objective of this application
is to support Dr. Manasi Agrawal’s career development into an independent patient-oriented investigator in the
field of molecular epidemiology of IBD. Dr. Agrawal’s career goal is to become a researcher and leader in the
identification of modifiable early-life risk factors for IBD, risk prediction and eventually, prevention of IBD. Dr.
Agrawal’s proposed training activities are in five areas: 1) advanced and life-course epidemiology, 2) advanced
biostatistical methodology 3) predictive biomarker analysis, 4) principles of immunological data analysis and 5)
scientific and grant writing. To achieve this, she has assembled a mentoring and advisory team led by Dr. Inga
Peter, Interim Chair of the Department of Genetics and Genomic Sciences at Mount Sinai and an expert in
translational -omics and data science, and Dr. Jean-Frederic Colombel, Director of the Feinstein IBD Center,
Mount Sinai, a global expert in clinical and translational investigation of IBD pathogenesis, prediction and
prevention. Environment: The Icahn School of Medicine at Mount Sinai has a strong tradition of outstanding
research and is one of the top 20 medical schools in NIH funding. The Mount Sinai Division of Gastroenterology
is consistently considered one of the top 10 divisions in the country by US News and World Report and is an
international leader in IBD research and clinical care. Research: IBD, including Crohn’s disease (CD) and
ulcerative colitis (UC), is a chronic, progressive, immune-mediated disease of the intestinal tract with significant
morbidity, healthcare costs and has no cure. IBD pathogenesis involves early-life risk factors, but these are not
well-understood, which impedes early intervention and prevention. Newer data suggest IBD is preceded by
intestinal inflammation, loss of microbiome diversity and distinct proteomic signatures. Developing IBD risk
prediction models will shed light on IBD pathogenesis, help identify at-risk individuals, and guide therapeutic and
preventive strategies. In addition, determining the impact of IBD risk factors on intestinal inflammation and
microbiome changes will provide further insights in IBD pathogenesis and the relevance of these changes.
Therefore, our specific aims are to (1) derive and validate models to predict CD and UC risk using early-life non-
genetic risk factors (2) determine if early-life IBD risk factors are associated with intestinal inflammation, and loss
of gut microbiome diversity as well as correlate IBD risk signature based on its prediction model with intestinal
inflammation (3) determine if inflammatory protein biomarkers in the cord serum are associated with maternal
IBD status and with intestinal inflammation in the mothers and their offspring. We will study the Danish
population-based cohort for Aim 1, and MECONIUM, a novel longitudinal cohort of pregnant women with and
without IBD and their offspring for Aims 2 and 3. The general approaches and skills developed during this award
can be applied to future studies to understand better IBD pathogenesis and toward preventive efforts.

Grant Number: 5K23DK129762-05
NIH Institute/Center: NIH
Principal Investigator: Manasi Agrawal