# Impact of benzalkonium chloride on gut microbiome and gut-liver interactions

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $648,691

## Abstract

Benzalkonium chlorides (BACs) are widely used antimicrobials in disinfecting products, medical products, and
food processing industries, suggesting humans may be exposed chronically to BACs through various routes.
The ongoing COVID-19 pandemic has led to greatly increased use of disinfectants, resulting in a 174% increase
in median BAC levels in human blood. We recently analyzed 15 de-identified human fecal samples collected
during COVID-19 and detected BACs in all of them, ranging from 55 nM to 2.74 µM (a 50-fold difference). BACs
are potent antimicrobials, but their effect on the gut microbiome has not been examined, which is the major gap
that this proposal aims to fill. Our goal is to characterize the effect of BAC exposure on gut microbiome compo-
sition and function, microbiota metabolism, and altered liver metabolism via the gut-liver axis. We previously
reported that BACs are metabolized by human cytochromes P450 (CYP) in the liver. Our preliminary data sup-
port biliary excretion from the liver to the intestine being the major route of elimination for BACs. Thus, exposure
of gut microbiome to BACs is inevitable regardless of the route of exposure. Disruption of the gut microbiome
can lead to changes in endogenous and xenobiotic metabolism through modulating the ligand availability for the
bile acid-sensing farnesoid X receptor (FXR), the lipid-sensing peroxisome proliferator-activated receptor-alpha
(PPARa), and xenobiotic-sensing constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Im-
portantly, in a preliminary study, we found that BAC exposure in mice significantly upregulated the expression of
Cyp2c38, Cyp2j6, Cyp4a10, and Cyp4f13 in the liver, which is consistent with the inhibition of CAR and/or acti-
vation of PPARa. Thus, we hypothesize that BACs reduce gut microbiome diversity and alter the metabolism of
xenobiotics, bile acids, sterols, and lipids in the liver by modulating the activities of nuclear receptors. In Aim 1,
we will characterize the impact of BAC exposure at different doses and exposure regimes on gut microbiome
diversity and function in mice. We will then correlate the changes in microbiome functional genes with the
changes in the gut bile acid, sterol, and lipid profiles. In Aim 2, we will measure the effect of BAC exposure on
bile acid, sterol, lipid, and xenobiotic metabolism in the liver of conventional and germ-free mice. Relationships
between bile acid, sterol, and lipid profiles and relevant gene expression levels in the liver will be evaluated.
Activation or inhibition of nuclear receptors regulating xenobiotic-metabolizing enzymes (XMEs) will be as-
sessed. In Aim 3, we will evaluate the relationship between BAC levels and gut microbiome diversity and function
in humans. The significance of this project lies in that it will allow us to begin to understand the impact of in-
creased BAC exposure on gut microbiome and gut-liver interactions in humans. The innovation of this project
lies in t...

## Key facts

- **NIH application ID:** 10799427
- **Project number:** 1R01ES035021-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Libin Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $648,691
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799427

## Citation

> US National Institutes of Health, RePORTER application 10799427, Impact of benzalkonium chloride on gut microbiome and gut-liver interactions (1R01ES035021-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10799427. Licensed CC0.

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