# Regulation of oxidative liver injury by the probiotic Lactobacillus rhamnosus GG

> **NIH NIH F30** · EMORY UNIVERSITY · 2021 · $50,351

## Abstract

Project Summary/Abstract
The gut microbiome is composed of a diverse and dynamic community of microorganisms in the intestinal
tract. Using germ-free model organisms, recent research has established the importance of these communities
in performing key metabolic, endocrine, and immunologic processes in the host. The majority of this research
has focused on the microbiome's effects on the intestine, the tissue with which it is in the most intimate
contact. Recent studies, however, have revealed that these effects are significantly more far-reaching, with
roles in hepatic, cardiovascular, and even neurological health. As the primary metabolic and detoxification hub,
the liver is a critical checkpoint between the digestive functions of the gut and the rest of the body. Therefore, it
is likely that alterations in the gut microbiota affect liver health and homeostasis. We utilized germ-free and
microbiome-replete mice to investigate the effects of the gut microbiome on liver metabolism. Analysis of
preliminary metabolomics data suggests significant alterations in hepatic metabolism, most notably in the
antioxidant and xenobiotic detoxification pathways classically controlled by the transcription factor Nrf2.
Activation of Nrf2 and its downstream pathways are cytoprotective against an array of oxidative liver insults,
including drug-induced liver injuries such as acetaminophen-induced hepatotoxicity. To extend these findings
beyond the artificial germ-free system, we propose to investigate the effect of microbiome manipulation on the
activation and functionality of these critical detoxification pathways. Our group has previously shown that the
widely studied probiotic Lactobacillus rhamnosus GG (LGG) can mediate protective effects in the intestine
through activation of the Nrf2 pathway. Based on these observations, we hypothesize that LGG induces Nrf2
signaling in the liver and that this is protective against oxidative liver injury. The specific aims of this proposal
are 1) to determine the extent of Nrf2 activation in the liver in response to LGG administration and 2) to identify
the effect of oral LGG administration on the pathogenesis of oxidative liver injury using a mouse model of
acetaminophen-induced hepatotoxicity. The long-term goal of this research is to understand the mechanisms
by which probiotics and the microbiome contribute to host homeostasis and disease.

## Key facts

- **NIH application ID:** 10187554
- **Project number:** 5F30DK117570-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Bejan Jon Saeedi
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $50,351
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187554

## Citation

> US National Institutes of Health, RePORTER application 10187554, Regulation of oxidative liver injury by the probiotic Lactobacillus rhamnosus GG (5F30DK117570-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10187554. Licensed CC0.

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