# Therapeutic mechanisms of L. lactis-mediated wound repair

> **NIH NIH K01** · EMORY UNIVERSITY · 2021 · $115,347

## Abstract

PROJECT SUMMARY:
The use of beneficial bacteria to promote intestinal health and to limit inflammation is widely practiced,
although experimental evidence corroborating the efficacy of many bacteria promoted with such claims
remains limited. We directly address this gap by identifying a newly characterized beneficial bacterium that
potently dampens injury-induced intestinal inflammation. In a screen of potential beneficial bacteria, we
identified Lactococcus lactis subsp. cremoris as a bacterium that elicited potent anti-inflammatory activity in the
mouse intestine. In order to substantiate the use of this strain as a therapeutic to treat IBD, which is required
‘Early Clinical Trial with Live Biotherapeutic Products’, we will take a rigorous approach to generate critical pre-
clinical data using relevant mouse models of colitis. Our preliminary data show that feeding of L. lactis elicits
lower Disease Activity Index (DAI) scores during chronic DSS treatment, and a significantly faster rate of
recovery following the withdrawal of DSS. Mechanistically, we show that L. lactis activates the cytoprotective
NRF2 signaling pathway in intestinal tissue, and show here that L. lactis-mediated protection, or Nrf2 gene
activation does not occur in Tlr2 & Myd88-null mice. Importantly, culture supernatant of L. lactis was sufficient
to accelerate healing in an in vitro epithelial cell wound healing model in cultured epithelial cells, indicating that
a factor secreted by L. lactis elicits the beneficial effects. Because phylogenetically related L. lactis ATCC
strains do not elicit the same beneficial effects, we hypothesize that a specific factor, bacterial
exopolysaccharide, within L. lactis is responsible for eliciting its powerful anti-inflammatory and pro-restitutive
effects via MyD88-dependent signaling. In addition, we show novel preliminary data that L. lactis activates the
expression of a specific set of microRNAs in intestinal tissue that are associated with the regulation of NRF2
pathway signaling. Therefore, our central hypothesis is that the specific element(s) released by L. lactis
induces cytoprotective and anti-inflammatory effects in the intestine, and can modulate the pathobiology of
IBD. We will test our hypothesis in the following specific aims: (1) to characterize the pro-restitutive effects of
L. lactis subsp. cremoris in colitis, (2) to identify the factor produced and released by L. lactis subsp. cremoris
that induces its beneficial effects and activates NRF2 signaling, and (3) to determine the role of key L. lactis
subsp. cremoris-induced microRNAs that regulate NRF2 signaling in modulating the cytoprotective effects of L.
lactis subsp. cremoris. Together, we identify an effector microorganism that beneficially influences host
phenotype, with clear favorable effects on dampening colitis-induced inflammation. We will discover the
underlying mechanisms of action, which has become foci of microbiome research, and which is essential for
the ...

## Key facts

- **NIH application ID:** 10301178
- **Project number:** 1K01DK127007-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** RHEINALLT MELFYN JONES
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $115,347
- **Award type:** 1
- **Project period:** 2021-09-03 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301178

## Citation

> US National Institutes of Health, RePORTER application 10301178, Therapeutic mechanisms of L. lactis-mediated wound repair (1K01DK127007-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10301178. Licensed CC0.

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