# Elucidating the pathological translocation mechanism(s) of a commensal bacterium in autoimmune liver disease

> **NIH NIH F30** · YALE UNIVERSITY · 2021 · $30,891

## Abstract

Project summary
The resident gut microbiota and the host immune system have co-evolved for millennia. However, modern
societal conditions have disturbed this co-evolution and this has coincided with a steep rise in immune-mediated
diseases. Bacterial translocation across the intestinal barrier and into extraintestinal organs such as the liver can
have major pathological consequences. Translocation of the commensal bacterium, Enterococcus gallinarum,
can trigger autoreactivity and chronic inflammation, contributing to autoimmune liver diseases such as
autoimmune hepatitis and primary sclerosing cholangitis. However, it is unknown how E. gallinarum in particular
is able to translocate across the epithelium and persist in normally sterile tissues such as the liver. Understanding
the exact mechanism(s) that enable E. gallinarum to cross the intestinal barrier could lead to the development
of novel therapeutic strategies to mitigate the initiation or progression of autoimmune liver disease. My
preliminary results suggest that E. gallinarum rapidly acquires the ability to translocate within the intestine after
monocolonization of germ-free mice. I hypothesize that spontaneous translocation of E. gallinarum to the liver
occurs when it acquires the ability to circumvent the host immune response in a gut microbiota background.
Here, I propose to: 1) test the hypothesis that E. gallinarum attains the capability to translocate by evading
immune surveillance; and, 2) determine whether specific gut commensals can hinder E. gallinarum translocation
via immunological priming. In the first aim, I will elucidate how E. gallinarum is able to evade host immune
response using a newly developed technology to profile differential binding of E. gallinarum isolates to host
extracellular proteins. In the second aim, I will perform in vivo colonization of E. gallinarum in the context of five
unique healthy human gut microbiotas, and determine the variability in resident gut microbiota-mediated host
immunological defense against E. gallinarum translocation. These studies will provide insight into the
fundamental mechanisms by which commensal bacteria translocate across the intestinal barrier and induce liver
autoimmunity. Thus, they may illuminate potential targets for novel therapeutic strategies for the treatment of
chronic autoimmune liver diseases that have major social, emotional, and financial costs and for which there are
currently no cures.

## Key facts

- **NIH application ID:** 10314725
- **Project number:** 1F30AI157227-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Mytien Nguyen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,891
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314725

## Citation

> US National Institutes of Health, RePORTER application 10314725, Elucidating the pathological translocation mechanism(s) of a commensal bacterium in autoimmune liver disease (1F30AI157227-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314725. Licensed CC0.

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