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Principal Investigator: Jayaraman, Arul
Institute Receiving Award Texas Engineering Experiment Station
Location College Station, TX
Grant Number R56ES033052
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 06 Sep 2022 to 31 May 2024
DESCRIPTION (provided by applicant): ABSTRACT The overall goal of the proposed work is to investigate the effects of xenoestrogens (XEs) on intestinal health. XEs, including bisphenol A (BPA), are an important classification of environmental contaminants that have the potential to influence gastrointestinal health. The role of estrogenic compounds on influencing colonic inflammation is complicated, but clinical and experimental data suggest that XEs exacerbate symptoms and markers of ulcerative colitis (UC), which is a highly prevalent disease state that requires medical intervention throughout life. Furthermore, data suggests that estrogenic compounds may serve as promoters of a subset of inflammation-associated colon tumors. While the effects of some estrogenic compounds (i.e. BPA) on the intestinal epithelium have begun to be explored, the extent to which microbiota influence their effects during inflammation remains an unresolved question. Identifying the role for the microbiota and discovering novel microbiota-derived estrogen receptor (ER) ligands would provide new evidence for an active role of the intestinal microbiota in mediating the effects of XEs through the ER beta (ERβ). The central hypothesis is that the intestinal microbiota plays a critical role in mediating the effects of XEs on intestinal health through de novo production and/or modification of ER ligands. Using wild type and ERβ intestinal specific knockout mice in conjunction with in vitro cultures and state-of-the-art metabolomics tools, the investigators will examine the microbiota-dependent and independent effects of XEs on intestinal health. The Specific Aims are: (i) Investigate the microbiota’s role in generating ER ligands following XE exposure; (ii) Determine the ER-mediated effects of XEs and microbiota-derived metabolites (MDMs) on colonic epithelial function; and (iii) Investigate the effect of XEs and microbiota-derived estrogens in exacerbating intestinal inflammation and subsequent colon tumor progression through the ER.
Science Code(s)/Area of Science(s) Primary: 68 - Microbiome
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications No publications associated with this grant
Program Officer Anika Dzierlenga
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