# A Novel Probiotic Engineered for Enhanced Immunological Function for Treating Inflammatory Bowel Disease

> **NIH NIH R43** · RISE THERAPEUTICS, LLC · 2020 · $216,963

## Abstract

Project Summary
The goal of this project is to commercialize a novel, immunologically-enhanced version of Lactobacillus
acidophilus for the treatment of inflammatory bowel disease (IBD).
Over 1.6 million adults and children in the United States suffer from IBD, an umbrella term encompassing two
chronic inflammatory diseases of the gastrointestinal tract: Crohn's disease (CD) and ulcerative colitis (UC)1.
IBD is typically diagnosed in the second or third decades of life and there is no cure. IBD is most commonly
treated with systemic immune suppressants or targeted cytokine blockers that can have serious side-effect
profiles including infection and cancer. Thus, new therapeutic strategies that are safe and effective, particularly
restoring the natural interaction between the immune system and gut microbiome, are needed and would be
life-changing for patients suffering from these difficult diseases.
Intestinal immune regulatory signals tightly govern healthy gut homeostasis. Breakdown of such regulatory
mechanisms may result in IBD2. The human microbiome is a critical regulator of these mechanisms.
Commensal bacteria function to maintain integrity of the intestinal epithelial barrier, as well as regulate innate
and adaptive immune cell function. One common bacterial species sold over the counter as a probiotic that
`promotes immune health' is Lactobacillus (L.) acidophilus. L. acidophilus contains unique surface layer
proteins (Slps), including SlpA, SlpB, SlpX, and lipoteichoic acid (LTA) that interact with pattern recognition
receptors (PRR; e.g., C-type lectin receptors) expressed on innate immune intestinal cells to regulate immunity
in steady state and disease conditions3-6.
Recently, our research team demonstrated that a novel L. acidophilus strain (termed R-2187) that is
reprogramed to selectively express SlpA, but not SlpB, SlpX and LTA, prevented experimentally induced colitis
in multiple disease animal models by inducing colonic T regulatory cells, reducing inflammation, improving the
intestinal membrane barrier, and restoring natural commensal flora7. SlpA binds to the C-type lectin Specific
Intracellular adhesion molecule-3 Grabbing Non-integrin homolog-Related 3 (SIGNR3) receptor expressed on
dendritic cells lining the gut. In contrast, protection was not observed in Signr3-/- mice, suggesting that SlpA
interaction with SIGNR3 plays a key protective role in regulating the disease condition7.
Our goal is to commercialize R-2187 as a novel, orally administered probiotic to reduce inflammation, improve
maintenance of gastrointestinal mucosal barrier function, and restore natural flora make-up in IBD patients.
The key objectives of this Phase I application are to: 1) produce a scale up batch of R-2187 and establish key
analytical assays, 2) perform in vitro functional assessment on human immune cells to characterize potential
biomarkers and create a potency assay, and 3) define the pharmacokinetics/pharmacodynamics relationship
and charact...

## Key facts

- **NIH application ID:** 9873907
- **Project number:** 5R43AI142975-02
- **Recipient organization:** RISE THERAPEUTICS, LLC
- **Principal Investigator:** Gary Fanger
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $216,963
- **Award type:** 5
- **Project period:** 2019-02-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873907

## Citation

> US National Institutes of Health, RePORTER application 9873907, A Novel Probiotic Engineered for Enhanced Immunological Function for Treating Inflammatory Bowel Disease (5R43AI142975-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873907. Licensed CC0.

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