# The impact of organophosphate flame-retardant exposure on metabolic and brain aging

> **NIH NIH R21** · TEXAS A&M AGRILIFE RESEARCH · 2024 · $409,508

## Abstract

PROJECT SUMMARY
Persistent organic pollutants such as organophosphate flame retardants (OPFRs) can accumulate in the body
and interact with nuclear receptors important in endocrine regulation. Given that OPFR exposure is pervasive
in the human population, there is a critical need to determine the impact of long-term exposure to OPFRs on
human health. Specifically, the impact of OPFR exposure on metabolic and brain aging remains undetermined.
Recent studies showed that perinatal exposure to an OPFR, triphenyl phosphate (TPHP), led to exacerbated
high fat diet-induced metabolic syndrome and gut dysbiosis. Notably, gut dysbiosis and the decrease in gut
barrier function have been associated with augmentation of systemic inflammation, metabolic dysfunction,
neuroinflammation and aging. Preliminary data from the lab showed an age-associated increase in facultative,
pro-inflammatory Proteobacteria, an indicator of epithelial cell dysfunction. Consistently, preliminary data
showed age-associated increases in gut permeability and systemic inflammation. Furthermore, using
untargeted serum metabolomics, tryptophan metabolism was identified as a signature pathway associated with
aging; remarkably, indole and indole-3-lactic acid, beneficial metabolites derived from the bacterial tryptophan
catabolism pathway, were significantly decreased with age. In addition, there were age-associated decreases
in fecal levels of butyric and propionic acids; these microbially produced short-chain fatty acids (SCFA) have
been shown to improve glucose homeostasis and insulin sensitivity. Importantly, new preliminary data
suggested that acute TPHP exposure in young adult mice exerted deleterious effects on colon epithelial cells,
with impaired barrier function and shifts in metabolism that favors colonization of facultative, pathogenic
bacteria. Together, these data provide a strong scientific premise for studying long-term effects of TPHP on the
microbiome-gut-brain axis in aging. The central hypothesis is that exposure to TPHP induces gut dysbiosis,
leading to gut barrier dysfunction, systemic inflammation, and neuroinflammation; these inflammatory
pathologies exacerbate aging-associated metabolic and cognitive decline. This exploratory hypothesis will be
tested by pursuing the following aim: Define the extent to which TPHP exposure contributes to metabolic and
cognitive decline. An aging cohort will be used, starting TPHP exposure from 10 months (M) of age as a mid-life
exposure model. Fecal microbiome, metabolome at 10, 15 and 18 M, in vivo metabolic and cognitive function at 13-15
M will be assessed in sub-Aim A, and, using these mice as donor mice, the causality of dysbiotic microbiota
induced by TPHP exposure in exacerbating metabolic and brain aging will be mechanistically tested via fecal
microbiota transplantation experiments in sub-Aim B. Senescence phenotypes in colon, liver, and brain will be
characterized in sub-Aim C. Overall, results will demonstrate the contri...

## Key facts

- **NIH application ID:** 10952637
- **Project number:** 1R21ES036683-01
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Chia-Shan Wu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,508
- **Award type:** 1
- **Project period:** 2024-09-16 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952637

## Citation

> US National Institutes of Health, RePORTER application 10952637, The impact of organophosphate flame-retardant exposure on metabolic and brain aging (1R21ES036683-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10952637. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*