New technologies for developing phage-based tools to manipulate the human microbiome
Open accessAbstract
Gut bacteria play an essential role in the human body by regulating multiple functions, producing essential metabolites, protecting against pathogen invasion, and much more. Conversely, changes in their community structure are linked to several gastrointestinal (GI) and non-GI conditions. Fortunately, these bacteria are amenable to external perturbations, but we need specific tools for their safe manipulation as nonspecific changes can cause unpredicted long-term consequences. Here, we mainly discuss recent advances in cultivation-independent technologies and argue their relevance to different key steps, that is, identifying the modulation targets and developing phage-based tools to precisely modulate gut bacteria and restore a sustainable microbiome in humans. We finally suggest multiple modulating strategies for different dysbiosis-associated diseases.
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Phages can eliminate cancer-associated bacteria.
“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 [63]
The “Phages as microbiota modulators” section (page unavailable) describes virulent phages as tools for eliminating unwanted bacteria. The section on disease-associated gut bacteria identifies *Helicobacter pylori*-associated gastric cancer, but the paper does not say that phages eliminate cancer-associated bacteria specifically. The claim applies a general proposed capability to a cancer setting that the cited paper does not establish. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPhages enable highly selective removal of cancer-associated bacteria within the gut or tumor niche, avoiding broad collateral damage to commensal communities associated with conventional antibiotics.
“In parallel, phages enable highly selective removal of cancer-associated bacteria within the gut or tumor niche (Table 1), avoiding the broad collateral damage to commensal communities associated with conventional antibiotics [15,17,20,62,63]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [63]
The “Phages as microbiota modulators” section says phages can target unwanted gut bacteria with high specificity while leaving nonhost bacteria unharmed. Figure 3 includes colorectal cancer among diseases for which phage-based microbiome modulation is a proposed goal. Our copy does not establish selective removal of cancer-associated bacteria in the gut or a tumor niche, or directly compare collateral damage with conventional antibiotics. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Muñoz-Benavent, M., Hartkopf, F., Bossche, T. V. D., Piro, V. C., García‐Ferris, C., Latorre, A., Renard, B. Y., & Muth, T. (2020) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaa058 · Cited by 21 · see citing works
Generation of a Metagenomics Proximity Ligation 3C Library of a Mammalian Gut Microbiota
Foutel-Rodier, T., Thierry, A., Koszul, R., & Marbouty, M. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.08.001 · Cited by 6 · see citing works
Flagged first, then by citations
1 of the 80 references couldn’t be matched to a known paper.
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Harnessing the plant microbiome for sustainable crop production
Compant, S., Cassán, F., KOSTIC, T. M., Johnson, L. J., Brader, G., Trognitz, F., & Sessitsch, A. (2024) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01079-1 · Cited by 387 · see citing works
Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C., & Laub, M. T. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01219-4 · Cited by 304 · see citing works
Structure, functions, and diversity of the healthy human microbiome
Ahrodia, T., Das, S., Bakshi, S., & Das, B. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2022.07.003 · Cited by 54 · see citing works
Phage Therapy in Germany—Update 2023
Willy, C., Bugert, J. J., Classen, A. Y., Deng, L., Duechting, A., Groß, J., Hammerl, J. A., Korf, I. H. E., Kühn, C., Lieberknecht-Jouy, S. C., et al. (2023) · Viruses · doi:10.3390/v15020588 · Cited by 49 · see citing works
Self-citationSpatial mapping of mobile genetic elements and their bacterial hosts in complex microbiomes
Grodner, B., Shi, H., Farchione, O., Vill, A. C., Ntekas, I., Diebold, P. J., Wu, D. T. S., Chen, C., Kim, D. M., Zipfel, W. R., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01735-5 · Cited by 47 · see citing works
Bacteriophage-mediated manipulations of microbiota in gastrointestinal diseases
Haddad, L. E., Mendoza, J. F., & Jobin, C. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1055427 · Cited by 40 · see citing works
Application of bacteriophages and endolysins in aquaculture as a biocontrol measure
Nachimuthu, R., Royam, M. M., Manohar, P., & Leptihn, S. (2021) · Biological Control · doi:10.1016/j.biocontrol.2021.104678 · Cited by 37 · see citing works
Microbiota-directed biotherapeutics: considerations for quality and functional assessment
Fekete, E. E. F., Figeys, D., & Zhang, X. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2186671 · Cited by 35 · see citing works
Advance on Engineering of Bacteriophages by Synthetic Biology
Sun, Q., Shen, L., Zhang, B., Yu, J., Wei, F. X., Sun, Y., Chen, W., & Wang, S. (2023) · Infection and Drug Resistance · doi:10.2147/idr.s402962 · Cited by 33 · see citing works
Role of gut microbiota and derived metabolites in cardiovascular diseases
Yu, J., Yang, Y., Chen, W., Hu, J., Jin, Z., Wu, C., & Li, Y. (2025) · iScience · doi:10.1016/j.isci.2025.113247 · Cited by 33 · see citing works
Emerging technologies in the study of the virome
Smith, S. E., Huang, W., Tiamani, K., Unterer, M., Mirzaei, M. K., & Deng, L. (2022) · Current Opinion in Virology · doi:10.1016/j.coviro.2022.101231 · Cited by 32 · see citing works
Self-citationBacteriophages, gut bacteria, and microbial pathways interplay in cardiometabolic health
Kirk, D., Costeira, R., Visconti, A., Mirzaei, M. K., Deng, L., Valdes, A. M., & Menni, C. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113728 · Cited by 30 · see citing works
Self-citationMassive expansion of the pig gut virome based on global metagenomic mining
Mi, J., Jing, X., Ma, C., Yang, Y., Li, Y., Zhang, Y., Long, R., & Zheng, H. (2024) · npj Biofilms and Microbiomes · doi:10.1038/s41522-024-00554-0 · Cited by 28 · see citing works
Luo, S., Ru, J., Mirzaei, M. K., Xue, J., Peng, X., Ralser, A., Mejías‐Luque, R., Gerhard, M., & Deng, L. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2257291 · Cited by 27 · see citing works
Self-citationYang, L., Li, X.-M., Duan, H.-Y., Yang, K., & Ye, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1398652 · Cited by 25 · see citing works
Mechanistic insights into the interaction between the host gut microbiome and malaria
Mandal, R. K., & Schmidt, N. W. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011665 · Cited by 15 · see citing works
Circadian Rhythm Modulation of Microbes During Health and Infection
Pearson, J. A., Voisey, A., Boest-Bjerg, K., Wong, F. S., & Li, W. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.721004 · Cited by 16 · see citing works
Metabolization of microbial postbiotic pentanoate drives anti-cancer CAR T cellsPreprint
Staudt, S., Nikolka, F., Perl, M., Franz, J., Leblay, N., Yuan, X.-K., Larrayoz, M., Lozano, T., Warmuth, L., Fante, M. A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.19.608538 · Cited by 14 · see citing works
Methods of DNA introduction for the engineering of commensal microbes
Liu, D., Siguenza, N., Zarrinpar, A., & Ding, Y. (2022) · Engineering Microbiology · doi:10.1016/j.engmic.2022.100048 · Cited by 14 · see citing works
Drug and gut microbe relationships: Moving beyond antibiotics
Kumbhare, S. V., Pedroso, I., Ugalde, J. A., Márquez‐Miranda, V., Sinha, R., & Almonacid, D. E. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103797 · Cited by 12 · see citing works
Concepts and criteria defining emerging microbiome applications
KOSTIC, T. M., Schloter, M., Arruda, P., Berg, G., Charles, T. C., Cotter, P. D., Kiran, G. S., Lange, L., Maguin, E., Meisner, A., et al. (2024) · Microbial Biotechnology · doi:10.1111/1751-7915.14550 · Cited by 12 · see citing works
Gut Phage Biobank: a collection of bacteriophages targeting human commensal bacteria
Xing, B., Liu, C., Chen, W., Li, Z., Jing, X., Wu, C., Liu, R., Zhang, X., Xu, X., Li, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61946-0 · Cited by 11 · see citing works
Exploring bacteriophages to combat gut dysbiosis: A promising new frontier in microbiome therapy
Easwaran, M., Abdelrahman, F. I., El‐Shibiny, A., Venkidasamy, B., Thiruvengadam, M., Sivalingam, P., Ganapathy, D. M., Ahn, J., & Shin, H. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.108008 · Cited by 9 · see citing works
Mapping the landscape of anti-phage defense mechanisms in the E. coli pangenomePreprint
Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C., & Laub, M. T. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.12.491691 · Cited by 9 · see citing works
Martínez, M., Rizzuto, I., & Molina, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094929 · Cited by 8 · see citing works
Exploring deep learning in phage discovery and characterization
Silva, M. K. D. P., Nicoleti, V. Y. U., Rodrigues, B. D. P. P., de Araújo, A. S. F., Ellwanger, J. H., Almeida, J., & Lemos, L. N. (2025) · Virology · doi:10.1016/j.virol.2025.110559 · Cited by 9 · see citing works
Phage-Microbiota Interactions in the Gut: Implications for Health and Therapeutic Strategies
Naderian, R., Alibabaei, F., Paraandavaji, E., Dehghan, P., & Eslami, M. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10784-z · Cited by 6 · see citing works
Zhang, Q., Li, J., Tuo, J., Liu, S., Liu, Y., Liu, P., Ye, L., & Zhang, X.-X. (2025) · The ISME Journal · doi:10.1093/ismejo/wraf051 · Cited by 6 · see citing works
Phage therapy in oncology: opportunities for cancer prevention and treatment
Mutalik, V. K., Inman, J. L., Chang, H., Arkin, A., & Mao, J.-H. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.02.001 · Cited by 5 · see citing works
Urbanowicz, M., Guziński, A., & Szulc, Z. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.02.673651 · Cited by 5 · see citing works
SVep1, a temperate phage of human oral commensal Streptococcus vestibularis
Wu, M., Zhu, Y., Yang, Y., Gong, Y., Chen, Z., Liao, B., Xiong, Y., Zhou, X., & Li, Y. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1256669 · Cited by 4 · see citing works
ProkBERT PhaStyle: accurate phage lifestyle prediction with pretrained genomic language models
Juhász, J., Ligeti-Nagy, N., Bodnár, B., Juhász, J., Pongor, S., & Ligeti, B. (2024) · Bioinformatics Advances · doi:10.1093/bioadv/vbaf188 · Cited by 4 · see citing works
Orlovska, I., Podolich, O. V., KUKHARENKO, O., Zubova, G., Reva, O. N., Cesare, A. D., Goés‐Neto, A., Azevedo, V., Barh, D., Vera, J.-P. P. D., et al. (2022) · Kosmìčna nauka ì tehnologìâ · doi:10.15407/knit2022.06.034 · Cited by 4 · see citing works
Li, C., Kou, R., Jia, Y., Fan, X., Shi, Y., & Chen, Q. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.00231-24 · Cited by 3 · see citing works
Supplementation and Elimination of Microbiome‐Produced Metabolites in the Treatment of Human Disease
Malogan, J., Hallowell, H., Francis, B., & Suez, J. (2025) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.70103 · Cited by 3 · see citing works
Microbiome alterations during and after international travel
DuPont, H. L. (2025) · Journal of Travel Medicine · doi:10.1093/jtm/taaf114 · Cited by 3 · see citing works
Ghadimi, D., Fölster‐Holst, R., Blömer, S., Ebsen, M., Röcken, C., Uchiyama, J., Matsuzaki, S., & Bockelmann, W. (2025) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2025.104967 · Cited by 2 · see citing works
vClean: assessing virus sequence contamination in viral genomes
Wagatsuma, R., Nishikawa, Y., Hosokawa, M., & Takeyama, H. (2024) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqae185 · Cited by 2 · see citing works
Microscopy methods map mobile genetic elements and their bacterial hosts
(2024) · Nature Microbiology · doi:10.1038/s41564-024-01774-y · Cited by 1 · see citing works
Ghadimi, D., Fölster‐Holst, R., Blömer, S., Ebsen, M., Röcken, C., Uchiyama, J., Matsuzaki, S., & Bockelmann, W. (2024) · PubMed Central · Cited by 1 · see citing works
Women in the European Virus Bioinformatics Center
Hufsky, F., Abecasis, A. B., Agudelo‐Romero, P., Bletsa, M., Brown, K. A., Claus, C., Deinhardt‐Emmer, S., Deng, L., Friedel, C. C., Gismondi, M. I., et al. (2022) · Viruses · doi:10.3390/v14071522 · Cited by 1 · see citing works
Self-citationSpatial Mapping of Mobile Genetic Elements and their Cognate Hosts in Complex MicrobiomesPreprint
Grodner, B., Shi, H., Farchione, O., Vill, A. C., Ntekas, I., Diebold, P. J., Zipfel, W. R., Brito, I., & Vlaminck, I. D. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.09.544291 · Cited by 1 · see citing works
Yang, X., Li, P., Zhang, Y., Wang, Z., Hu, D., Li, Y., Hu, Z., Deng, L., Wang, X., & Ru, J. (2025) · Research Square · doi:10.21203/rs.3.rs-6913311/v1 · Cited by 1 · see citing works
Self-citationExploring the Hidden Potential of Bacteriophages 3-Part Miniseries
Ilieva, N., & Nemecek, A. (2023) · Journal of Student Research · doi:10.47611/jsrhs.v11i1.2386
Microbiome subtractive therapy for health benefits
Sengupta, A. M., Choudhary, M. K., & Chattopadhyay, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99336-4.00015-x
The Role of Gut Microbiota in Psoriasis: Current Knowledge and Emerging Therapeutic Interventions
Memariani, H., & Memariani, M. (2024) · International Journal of Enteric Pathogens · doi:10.34172/ijep.5636
A Lambda-evo (λevo) phage platform for Zika virus EDIII protein display
Negrete-Méndez, H., Valencia-Toxqui, G., Martínez-Peñafiel, E., Contreras, O. M., Fernández‐Ramírez, F., Morales‐Ríos, E., Navarro-González, L. J., Torres-Flores, J. M., & Kameyama, L. (2025) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-024-13380-3
THE GUT MICROBIOME AND ITS ROLE IN HUMAN HEALTH
Hawryluk, A., Urbańska, K., Żuczek, A., Dyndał, K., Broda, M., Żuczek, O., Szczap, I., Marzec, K., Mokrzycka, A., & Jędrzejewska-Rzezak, P. (2025) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(47).2025.3888
Site‐ and age‐dependent associations between Fusobacterium nucleatum and colorectal cancer mortality
Lorona, N. C., LaBrie, S. D., Thomas, C. E., Yin, H., Huyghe, J. R., Qu, C., Thomas, S., Nayemi, S., Ammar, H., Kahsai, O. J., et al. (2026) · Cancer · doi:10.1002/cncr.70484
Microfluidic encapsulation of the human gut microbiota—a tool for research and beyond
Wheatley, S. K., Dupeyroux, L., Rodger, M., Hamoud-Michel, H., Boutin, T., Prattico, C., Lerouge, S., Maurice, C. F., & Ahmadi, A. (2026) · Microsystems & Nanoengineering · doi:10.1038/s41378-026-01264-7
Microbiome-Based Therapies: Phage Intervention
Hadi, J. L., Thaqi, A., Ammann, J., Mirzaei, M. K., & Deng, L. (2026) · Springer eBooks · doi:10.1007/978-3-032-26410-7_23
Self-citationPost‐Microbial Therapeutics for the Next Generation of Medicine
Bhuiyan, M. N. I., & Momtaj, M. (2026) · MicrobiologyOpen · doi:10.1002/mbo3.70427
- Authors
- Khan Mirzaei, M., & Deng, L.
- Affiliations
- Helmholtz Munich (DE)
- Corresponding author
- Deng, Li
- ORCID
- Deng, Li
- Venue
- Trends in Microbiology
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 30
- Issue
- 2
- Pages
- 131-142
- ISSN
- 0966-842X (ISSN-L)
- OpenAlex
- W3163713499
- Cited by
- 53
- References
- 80
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 15 · 2023: 10 · 2022: 8 · 2021: 2
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in Microbiology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- Funders
- European Research Council (ERC StG 803077)
- Deutsche Forschungsgemeinschaft (273124240, 395357507)
- Technical University of Munich (SFB 1371)
- Helmholtz Zentrum München Deutsches Forschungszentrum für Umwelt und Gesundheit
- Topics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- bacteriophages, human gut microbiome, microbiota modulation, dysbiosis, gut microbiota, microbiota restoration
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Bacteriophages, Humans, Microbiota, Dysbiosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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