# Development of a therapeutic bacterial consortium for constipation

> **NIH NIH R43** · HOLOBIOME, INC. · 2021 · $299,600

## Abstract

The goal of the proposed project is to develop a probiotic for the treatment of constipation, comprised of 2-3 anti-
inflammatory strains of human gut-derived bacteria that enhance host serotonin (5-hydroxytryptamine, 5-HT)
production and signaling. By addressing multiple targets associated with the etiology and symptoms of
constipation (5-HT signaling and inflammation), we expect the result of this project to have broad utility.
Constipation affects up to 20% of the general population, with rates even higher in the elderly, and comes in
many forms ranging in severity. The most severe form, slow transit constipation (STC), affects ~15 to 30% of
constipated patients. Less severe, but still representing a significant societal burden, are irritable bowel
syndrome with constipation (IBS-C) and age-associated constipation. Constipation is also a major side effect of
opioid medications, and is comorbid with neurological diseases including Parkinsonian syndromes. The etiology
is multifarious, often involving a dysfunctional enteric nervous system, poor diet, and inflammation, but in many
cases it is still poorly understood. Current treatment options are generally poor and include dietary modifications,
pharmacological interventions, and—for severe forms like STC—surgery. As such, novel treatment options are
needed, preferably those that can engage multiple therapeutic targets. One source of new therapeutics is the
gut microbiome: the bacteria that reside in the gastrointestinal tract. These symbiotic organisms are involved in
numerous components of health and disease, including development and maintenance of the immune and
enteric nervous systems. Recently, it has been shown by a member of Holobiome’s team that the gut microbiome
is a major regulator of host enteric 5-HT signaling: Germ free mice have a 50% reduction in serum 5-HT and
have constipation, both of which can be corrected via recolonization with a normal microbiome or a human-
derived consortium. It has also been shown that constipation in humans can be transferred into animals via fecal
microbiome transplant; a phenotype that is driven via disrupted enteric 5-HT signaling and inflammation. This
suggests a clear intervention strategy: deliver anti-inflammatory, 5-HT-modulating bacteria to the gut. In our
preliminary studies we screened a proprietary panel of over 100 non-pathogenic species of human gut bacteria
for the ability to modulate 5-HT in a cell culture model. We identified 17 bacterial strains with the capability to
modulate 5-HT signaling via four mechanisms. In this Phase 1 application we seek to further test these strains
as candidates for a 5-HT modulating and anti-inflammatory consortium. To do this, strains will first be profiled for
safety and manufacturability in vitro and in silico. Strains meeting these criteria will be assembled into candidate
consortia of 2-3 strains, which will be further optimized to impact 5-HT release and inflammation. These will be
advanced for test...

## Key facts

- **NIH application ID:** 10254559
- **Project number:** 1R43DK127864-01A1
- **Recipient organization:** HOLOBIOME, INC.
- **Principal Investigator:** Philip Peter Strandwitz
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,600
- **Award type:** 1
- **Project period:** 2021-07-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254559

## Citation

> US National Institutes of Health, RePORTER application 10254559, Development of a therapeutic bacterial consortium for constipation (1R43DK127864-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10254559. Licensed CC0.

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