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Published on: January 26, 2024
Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts
Kosuke Fujimoto1, Yasumasa Kimura2, Masaki Shimohigoshi3
1Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Division of Metagenome Medicine, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan.
Abstract:
The application of bacteriophages (phages) is proposed as a highly specific therapy for intestinal pathobiont elimination. However, the infectious associations between phages and bacteria in the human intestine, which is essential information for the development of phage therapies, have yet to be fully elucidated. Here, we report the intestinal viral microbiomes (viromes), together with bacterial microbiomes (bacteriomes), in 101 healthy Japanese individuals. Based on the genomic sequences of bacteriomes and viromes from the same fecal samples, the host bacteria-phage associations are illustrated for both temperate and virulent phages. To verify the usefulness of the comprehensive host bacteria-phage information, we screened Clostridioides difficile-specific phages and identified antibacterial enzymes whose activity is confirmed both in vitro and in vivo. These comprehensive metagenome analyses reveal not only host bacteria-phage associations in the human intestine but also provide vital information for the development of phage therapies against intestinal pathobionts.
Insights
Bacteriophages (phages) show promise for eliminating gut pathogens. This study maps phage-host interactions in the human gut microbiome, aiding the development of targeted phage therapies against harmful bacteria.
Area of Science:
- Microbiology
- Virology
- Genomics
Background:
- Bacteriophages (phages) are viruses that infect bacteria and are being explored for targeted pathogen elimination.
- Understanding phage-host interactions within the human gut microbiome is crucial for developing effective phage therapies.
- Previous research has not fully elucidated the complex associations between phages and bacteria in the intestinal environment.
Purpose of the Study:
- To characterize the intestinal viromes and bacteriomes in a cohort of healthy individuals.
- To identify and map host bacteria-phage associations within the human gut.
- To demonstrate the utility of this data for identifying phages and enzymes effective against specific pathogens like Clostridioides difficile.
Main Methods:
- Collected fecal samples from 101 healthy Japanese individuals.
- Performed metagenomic sequencing of both viral (viromes) and bacterial (bacteriomes) communities.
- Analyzed genomic data to determine host bacteria-phage associations for both temperate and virulent phages.
Main Results:
- Detailed mapping of host bacteria-phage associations in the human intestinal microbiome.
- Identification of specific phages targeting Clostridioides difficile.
- Validation of antibacterial enzyme activity in vitro and in vivo.
Conclusions:
- Comprehensive metagenomic analysis provides essential insights into gut phage-host dynamics.
- This data is vital for the development of precision phage therapies against intestinal pathobionts.
- The study validates the potential of phage-based strategies for combating bacterial infections.
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