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Novel effects of xenoestrogens and gut microbiota derived estrogenic compounds in colonic inflammation

Award Number: R56ES033052
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Novel effects of xenoestrogens and gut microbiota derived estrogenic compounds in colonic inflammation - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$366 )
2025	2022	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Environmental Health	000	1	1/3/2025	NEW	-$366
														Subtotal = -$366

Issue Date FY: 2022 ( Subtotal = $374,998 )
2022	2022	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Environmental Health	000	1	9/5/2022	NEW	$374,998
														Subtotal = $374,998

Grand Total All Awards = $374,632

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Novel effects of xenoestrogens and gut microbiota derived estrogenic compounds in colonic inflammation

Award Number: R56ES033052

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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