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A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System
Published on: August 30, 2019
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Reduction of product composition variability using pooled microbiome ecosystem therapy and consequence in two
Julie Reygner1, Johanne Delannoy2, Marie-Thérèse Barba-Goudiaby3
1MaaT Pharma, Lyon, France.
Applied and Environmental Microbiology
|April 23, 2024
Summary
Pooled fecal microbiotherapy enhances gut microbiota homogeneity and diversity, improving efficacy against infections like Clostridioides difficile compared to single-donor treatments.
Area of Science:
- Microbiome research
- Microbiota therapeutics
- Gut health and disease
Background:
- The gut microbiota plays a crucial role in human health and disease.
- Microbiotherapy shows promise for conditions linked to gut dysbiosis, including infections and inflammatory diseases.
- Variability in single-donor fecal products limits reproducibility and efficacy.
Purpose of the Study:
- To compare the metagenomic profiles and therapeutic efficacy of pooled versus single-donor fecal microbiotherapy products.
- To assess the impact of pooling on microbiota homogeneity, diversity, and beneficial bacteria content.
- To evaluate the effectiveness of pooled products in preclinical models of bacterial infections.
Main Methods:
- Metagenomic analysis of pooled and single-donor fecal products.
- In vivo studies using mouse models of Salmonella and Clostridioides difficile infections.
- In vitro growth inhibition assays against drug-resistant bacteria (Enterococcus faecium vanA, Klebsiella pneumoniae oxa48).
Main Results:
- Pooled products exhibited greater homogeneity, diversity, and enrichment of beneficial bacteria producing anti-inflammatory short-chain fatty acids.
- Pooled fecal microbiotherapy significantly reduced pathogenicity in Salmonella and C. difficile mouse models.
- Single-donor product efficacy was variable, with some failing to control disease progression.
- Pooled products demonstrated efficacy against drug-resistant bacterial strains in vitro.
Conclusions:
- Pooling fecal donors homogenizes product composition, increases microbial diversity, and enhances therapeutic efficacy.
- Pooled fecal microbiotherapies offer a more consistent and effective treatment strategy compared to single-donor products.
- These findings support the development of pooled microbiotherapies to overcome donor-dependent variability and improve treatment outcomes for gut dysbiosis-related conditions.
