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Phages and their potential to modulate the microbiome and immunity
Open accessAbstract
Bacteriophages (hence termed phages) are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection. However, the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades, limiting their therapeutic application. While many phages and their functional repertoires remain unknown, the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria. Furthermore, the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation. Importantly, the narrow host range, immense antibacterial repertoire, and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic, commensal and pathobiont members of the microbiome, thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiome-associated diseases. In this review, we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage-bacteria-host interactions may facilitate the development of novel phage-based therapeutics. We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.
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“Phages can eliminate cancer-associated bacteria, remodel the tumor microenvironment, enhance antitumor immunity, and deliver targeted therapeutic payloads.”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [21]
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“Additionally, phage DNA and structural proteins engage pattern recognition receptors within innate immune pathways, thereby enhancing antitumor immune responses [21,23–26]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [21]
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“Indirectly, phages reshape tumor-associated bacterial communities, depleting protumorigenic taxa and altering microbial metabolites that regulate inflammation, genotoxic stress, and therapeutic response [20–23]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [21]
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“Indirectly, phages reshape tumor-associated bacterial communities, depleting protumorigenic taxa and altering microbial metabolites that regulate inflammation, genotoxic stress, and therapeutic response [20–23]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [21]
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“Indirectly, phages reshape tumor-associated bacterial communities, depleting protumorigenic taxa and altering microbial metabolites that regulate inflammation, genotoxic stress, and therapeutic response [20–23]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [21]
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“Studies have begun uncovering direct and indirect immunomodulatory properties of phages beyond their antimicrobial effects [21,25,74]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [21]
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Metadata
- Authors
- Federici, S., Nobs, S. P., & Elinav, E.
- Affiliations
- Weizmann Institute of Science (IL)
- German Cancer Research Center (DE)
- Corresponding author
- Elinav, Eran
- Venue
- Cellular & Molecular Immunology
- Published
- 2020-09-08
- Volume
- 18
- Issue
- 4
- Pages
- 889-904
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC8115240
- OpenAlex
- W3084223430
- Cited by
- 222
- References
- 242
- Citations by year
- 2026: 49 · 2025: 55 · 2024: 42 · 2023: 38 · 2022: 26 · 2021: 12
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- bacteriophages, phage therapy, human microbiome, phage-bacteria interactions, antibiotic resistance, immunomodulation, mucosal immunity, commensal bacteria, pathobionts, phage vectors
- MeSH terms
- Phage Therapy, Animals, Bacteria, Bacterial Infections, Bacteriophages, Humans, Drug Resistance, Multiple, Bacterial
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