# Bacteria-associated VB12 regulates neonatal ileal epithelium homeostasis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $343,125

## Abstract

Project Summary/Abstract
Incidence of pediatric inflammatory bowel disease (IBD) is increasing worldwide. The causative mechanisms
involved in the disease pathogenesis are currently elusive. However, induced pathogenic inflammation due to
malnutrition, impacting the ileal epithelium homeostasis, may contribute to disease manifestation. Thus,
understanding the dietary risk factors involved in pediatric IBD is urgent. Diet containing micronutrients (e.g.,
vitamins) functionally controls the genomic mechanisms of the neonatal intestinal cells. Deficiency in host
nutritional circuitry, notably during the pre and postnatal periods of pregnancy may not only impair the host-
bacteria interaction controlling the gut homeostasis but also deteriorate the metabolic networks required for
bacterial syntrophic growth. Vitamin B12 (VB12) is synthesized by some intestinal bacteria. VB12 deficiency may
dysfunction ileal epithelial cells (iECs) expressing VB12 receptors (e.g., cubilin, megalin) with severe intestinal
disorders post-birth. We recently reported that the newly discovered Propionibacterium strain, P. UF1, regulates
phagocytic and protective T cell responses to intestinal pathogen infection in newborn and adult mice. Further,
P. UF1 produces VB12 and crucially controls the biosynthesis of this vitamin through a novel putative riboswitch,
cbiMCbl. We now demonstrate that VB12 critically controls ileal epithelial cell (iEC) molecular and metabolic
homeostasis, particularly the mitochondrial respiration, to potentially limit aerobic Salmonella (STm) infection in
newborn mice. The objectives of this research proposal are to further elucidate that (a) VB12 functionally sustains
iEC function during STm infection, (b) VB12 regulates oxygen levels in iECs resulting in luminal hypoxia that
controls aerobic STm infection and (c) VB12 fortifies ileal epithelium integrity and supports effector T helper (Th)
cell response to STm challenge. The overarching hypotheses are: (1) VB12 reprograms the molecular machinery
of iECs during STm infection, (2) regulation of ileal oxygenation by VB12 induces the luminal hypoxia that limits
the aerobic STm infection and (3) controlling iEC-function by VB12 contributes to epithelial integrity and
protective Th cell response to aerobic STm infection. The following Specific Aims will test these hypotheses: 1.
Elucidate the molecular mechanisms sustaining iEC function by VB12 during STm infection. 2. Elaborate on the
mitochondrial oxygen regulation in iECs by VB12 controlling aerobic STm infection. And 3. Investigate barrier
integrity regulation by VB12 and protective Th cell response to STm infection. Results obtained from the
proposed mechanistic studies will be the first in-depth report underscoring VB12 potency in regulating iEC
function for a sustainable therapeutic strategy that could potentially improve neonatal health.

## Key facts

- **NIH application ID:** 10117335
- **Project number:** 2R01DK109560-05A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Mansour M Zadeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,125
- **Award type:** 2
- **Project period:** 2016-05-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117335

## Citation

> US National Institutes of Health, RePORTER application 10117335, Bacteria-associated VB12 regulates neonatal ileal epithelium homeostasis (2R01DK109560-05A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10117335. Licensed CC0.

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