Newly discovered gut viruses reshape understanding of the microbiome

Newly discovered gut viruses reshape understanding of the microbiome

Scientists have uncovered new details about viruses that live inside bacteria in the human gut, challenging long held assumptions about how dynamic the microbiome really is.

Using advanced long read DNA sequencing, researchers tracked viral DNA embedded within gut bacteria in healthy adults over a two year period. These viruses, known as prophages, are bacteriophages that insert their genetic material into bacterial genomes.

The study found that most gut viruses are remarkably stable, remaining inside the same bacterial hosts for years. Only a small fraction were gained or lost over time, suggesting that the gut microbiome is more steady and predictable than previously thought.

Researchers also discovered that some viruses can live in multiple types of bacteria, contradicting the idea that phages are usually limited to a single host.

A key finding was the discovery of a new group of prophages called IScream phages. These viruses use bacterial mobile DNA elements to insert and remove themselves from host genomes, revealing a previously unknown mechanism of viral integration. This suggests gut viruses may be more genetically flexible than scientists realized.

The findings were made possible by long read sequencing technology, which allows scientists to assemble complete bacterial genomes and precisely locate viral DNA, something earlier methods could not do reliably.

Experts say the work reshapes understanding of how viruses influence gut health and could have long term implications for microbiome based therapies, including treatments targeting digestive, immune, and metabolic diseases.

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We are pleased to announce that the 9th Annual Meeting Targeting Phage Therapy 2026 will be held in Valencia, Spain, on June 11–12. We look forward to welcoming you.

Concluding Remarks : Targeting Phage Therapy 2025 did not close a chapter. It opened a new one

Concluding Remarks : Targeting Phage Therapy 2025 did not close a chapter. It opened a new one

Targeting Phage Therapy 2025 marked a decisive moment for the field of phage therapy. What was once viewed mainly as an experimental or compassionate use approach has clearly entered a new phase, one defined by clinical structuring, regulatory engagement, and growing industrial readiness.

Over two days in Berlin, the conference brought together clinicians, researchers, regulators, and industry leaders from around the world. A clear and shared message emerged throughout the meeting: phage therapy is no longer just a scientific promise. It is becoming a clinical necessity.

The program highlighted tangible progress in human clinical trials, including applications in cystic fibrosis, burn wounds, cardiothoracic surgery related infections, and multidrug resistant pathogens. Participants also shared major advances in delivery technologies, ranging from inhaled formulations to hydrogels and biohybrid systems. Discussions reflected a growing maturity in GMP production, with concrete examples of hospital-based manufacturing pipelines and improved quality control strategies.

There was also an unprecedented focus on regulatory frameworks, national guidelines, and the need for European harmonization. Importantly, the scope of phage therapy was shown to extend well beyond human medicine, with expanding applications in veterinary health, agriculture, food safety, and industry.

Throughout the discussions, it became clear that the future of phage therapy will depend on collaboration rather than fragmentation. Progress will require stronger bridges between hospitals and industry, between regulators and innovators, and between microbiology and clinical medicine.

The final panel highlighted several critical priorities for the coming years. These include scaling access to phage therapy while maintaining safety and quality, structuring personalized phage approaches within clear regulatory pathways, building shared infrastructures such as phage banks and clinical networks, and strengthening dialogue across science, medicine, and industry.

Targeting Phage Therapy 2025 did not close a chapter. It opened a new one.

With this momentum, the community now looks ahead to 2026 with a shared ambition: to move phage therapy from pioneering cases to structured, accessible, and impactful solutions for health and industry.

Award Recipients Recognized for Innovation and Excellence

The conference recognized outstanding contributions to the field:

  • Poster Presentation Award: Peter Braun and Leonie Reetz (Fraunhofer ITMP, Germany)
  • Poster Presentation Award: Viviane de Cássia Oliveira
  • Poster Presentation Award: Miriam Waizer (University of Regensburg, Germany)
  • Short Oral Award: Anthony Vocat (Lausanne University Hospital, Switzerland)
  • Best Innovation Award: José Luis Bila(Precise Health SA, Switzerland)

Phage Therapy 2025 Awards.

The 9th Annual Meeting will be held in Valencia, Spain on June 11-12, 2016. See you soon!

New research shows bacteriophages can cross the intestinal barrier even in healthy conditions

New research shows bacteriophages can cross the intestinal barrier even in healthy conditions

A new study published in Cell Reports shows that bacteriophages, the viruses that infect bacteria, can pass through the intestinal lining under normal physiological conditions. Researchers tested three different phages and found that all were able to move across gut epithelial cells without inflammation or damage to the barrier.

This finding challenges the long standing belief that phages only enter the body when the gut barrier is compromised, such as during inflammatory bowel disease. Instead, the results suggest that phage movement from the gut into the body may be a natural process, opening new perspectives on how phages interact with the immune system and influence human health.

Bacteriophage RNA: A Tiny Viral RNA Tips the Balance Between Life and Death in Infected Bacteria

Bacteriophage RNA: A Tiny Viral RNA Tips the Balance Between Life and Death in Infected Bacteria

A tiny viral RNA can decisively tip the balance between life and death in infected bacteria.

In a study published in Molecular Cell, researchers report that bacteriophage lambda uses a short regulatory RNA—named PreS—to hijack its host’s DNA replication machinery. Rather than relying only on viral proteins, the phage deploys this small RNA to reprogram E. coli from the inside.

PreS binds to the bacterial messenger RNA of dnaN, a gene that encodes the β sliding clamp, an essential component of DNA replication. By reshaping the mRNA’s structure, the viral RNA boosts production of the clamp, effectively supplying the virus with more of the tools it needs to rapidly copy its own genome.

When PreS is removed or its binding site disrupted, viral replication slows and the destructive, lytic phase of infection is delayed. The finding reveals an unexpected layer of viral control and suggests that small RNAs may be common — and powerful — weapons in phage infections.

Beyond basic biology, the work could inform future phage therapy strategies, where understanding and tuning viral replication is key to turning bacteria’s natural predators into reliable medical tools.

Clinical Application of Bacteriophage Therapy in Children

Clinical Application of Bacteriophage Therapy in Children

Bacteriophage therapy, which uses viruses that target specific bacterial pathogens, is being considered as a potential alternative to antibiotics, particularly for pediatric patients with multidrug-resistant infections.

This approach offers the advantage of targeting only the harmful bacteria, reducing the disruption to the child’s microbiome commonly seen with antibiotics. Bacteriophages can be applied topically or systemically, depending on the type and location of the infection. Research is focused on refining the use of bacteriophages for both acute and chronic infections in children, with ongoing work to address challenges such as selecting the appropriate phage for each infection and ensuring long-term effectiveness.

In this context, John S. Bradley from the University of California San Diego has contributed to the discussion of how bacteriophage therapy may complement traditional antibiotics and offer a more targeted approach to treating infections that are difficult to manage with standard treatments.

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Image Credit: Freepik.com

Bacteriophage Therapy: A New Approach for Severe Bacterial Infections

Bacteriophage Therapy: A New Approach for Severe Bacterial Infections

 Bacteria acquire phage resistance.

The increasing prevalence of antibiotic-resistant bacteria presents a critical global health challenge. According to the WHO, 1.27 million deaths in 2019 were linked to resistant infections, and by 2050, fatalities from these infections are projected to exceed those caused by cancer.

The Role of Phage Therapy

As an alternative to antibiotics, bacteriophage (phage) therapy utilizes viruses that specifically target and eliminate bacteria. This approach has shown promise in treating severe infections, particularly those caused by multidrug-resistant (MDR) bacteria:

  • Successful treatment of patients with panresistant Pseudomonas aeruginosa
  • Recovery from systemic Acinetobacter infections following phage administration

Advantages and Challenges

Key benefits of phage therapy include:

  • High specificity – Targets only the harmful bacteria, preserving the microbiome
  • Potential synergy with antibiotics – May enhance treatment effectiveness

Challenges and ongoing research efforts:

  • Bacterial resistance to phages – Addressed through phage selection and combination strategies
  • Phage specificity – Requires precise matching of phage to bacterial strain

Global Developments in Phage Therapy

  • Belgium has established a national phage bank to facilitate clinical applications.
  • The United States is advancing research through Innovative Phage Applications and Therapeutics (IPATH) at UC San Diego.

Phage therapy is emerging as a key component of personalized medicine, offering a promising treatment option for patients with life-threatening bacterial infections. Continued research and clinical trials are essential to further establish its role in combating antibiotic resistance.

Figure Description: There are several mechanisms through which bacteria can gain resistance to phages, as follows: ① mutation or modification of surface receptors, ② the CRISPR‒Cas system, ③ restriction-modification system, and ④ abortive infection

Article DOI.

Image Credit: Sawa, T., Moriyama, K. & Kinoshita, M. j intensive care 12, 44 (2024). 

KlebPhaCol: Revealing the Gut’s Hidden Phage Potential in Klebsiella Research

KlebPhaCol: Revealing the Gut’s Hidden Phage Potential in Klebsiella Research

The human gut is a complex ecosystem where bacteriophages play a crucial but often overlooked role. Now, KlebPhaCol, a community-driven resource developed by Franklin L. Nobrega and colleagues, provides a comprehensive collection of 53 phages and 74 Klebsiella isolates, offering valuable insights into phage-bacteria interactions in the gut.

One of the most exciting discoveries is a novel gut phage order, Felixvirales, linked to the human microbiome. These phages span five families, targeting 27 sequence types (including ST258, ST11, and ST14) and 28 capsular-locus types (such as KL1 and KL2) across six Klebsiella species. Given Klebsiella’s role in gut colonization and antibiotic resistance, this research provides a new foundation for developing bacteriophage-based therapies.

Freely accessible at www.klebphacol.org, KlebPhaCol invites researchers worldwide to explore and expand this resource, fostering collaboration in the fight against multidrug-resistant pathogens.

Access preprint: DOI: 10.1101/2024.12.02.626457

The Hidden Architects of the Gut: Phage-Bacteria Dynamics in Early Childhood Development

The Hidden Architects of the Gut: Phage-Bacteria Dynamics in Early Childhood Development

A schematic of factors potentially accounting for high virus (phage) turnover in human guts.

This study explores the dynamic relationship between bacteriophages (phages) and bacteria in the gut microbiome of infants and young children during their early years. Using metagenomic sequencing data from over 12,000 stool samples collected as part of the Environmental Determinants of Diabetes in the Young (TEDDY) project, the researchers uncovered how phages and bacteria interact and evolve. Phages, described as the “hidden architects” of the gut ecosystem, exhibit faster turnover and greater transience than bacteria while accumulating diversity over time.

The analysis revealed structured ecological succession in the microbiome, with microbial communities transitioning through distinct phases as children age. It was found that children who later developed type 1 diabetes showed slower changes in their microbial community during their second year of life. By employing the novel bioinformatics tool Marker-MAGu, the study enabled simultaneous profiling of phages and bacteria, revealing a deeper understanding of their co-evolution. Phage profiling also improved the ability to geographically distinguish microbiomes, underscoring their role in shaping microbial ecosystems.

These findings highlight the crucial yet underappreciated role of phages in gut microbiota development and their potential influence on immune system maturation and disease risk. This work not only provides valuable insights into the early-life gut microbiome but also paves the way for phage-based therapeutic and diagnostic strategies.

Figure Description: Since phage often put negative selective pressure on their hosts, these bacteria may evolve evasive mutations in receptor-related genes or other entry factors. Relatedly, some bacteria can conduct phase variation, reversibly altering their surface molecules. Bacteria may also acquire phage-specific CRISPR spacers to fend off deleterious phage or acquire entirely new phage defence systems via horizontal gene transfer. Phage, on the other hand, will sometimes, but not always overcome these new defences via mutation of their own genes. In our study, we are unable to detect bacterial strain switching, in which a new strain of the same bacteria interlopes and outcompetes an existing strain. Strain switching will cause some or all of the bacteria-specific phage to be lost from the gut due to different receptors and defence systems, but it will provide opportunities for new phages. Finally, if a bacterial host becomes extinct, so will its obligate parasite phage, so phages are not expected to persist in the gut for long periods after elimination of its host.

Image Source: Tisza, M.J., Lloyd, R.E., Hoffman, K. et al. Nat Microbiol (2025)

Article DOI: https://doi.org/10.1038/s41564-024-01906-4

Personalized Bacteriophage Therapy: Insights from 100 Consecutive Cases

Personalized Bacteriophage Therapy: Insights from 100 Consecutive Cases

Jean-Paul Pirnay and his team from the Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium, and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Non-traditional Antibacterial Therapy (ESGNTA), Basel, Switzerland, have presented a detailed analysis of personalized bacteriophage therapy (BT) outcomes. This retrospective observational study analyzed the first 100 consecutive cases of personalized BT for difficult-to-treat infections. The cases were facilitated by a Belgian consortium across 35 hospitals, 29 cities, and 12 countries between January 1, 2008, and April 30, 2022.

In contrast to the limited success observed in randomized controlled trials with non-personalized bacteriophage products, this study highlights promising outcomes for personalized approaches. The researchers evaluated general efficacy and conducted a regression analysis to explore functional relationships. Key findings include:

  • Clinical Improvement: 77.2% of infections showed clinical improvement following personalized BT.

  • Bacterial Eradication: Targeted bacteria were eradicated in 61.3% of infections.

  • Impact of Concomitant Antibiotics: The absence of concomitant antibiotics reduced the likelihood of bacterial eradication by 70% (odds ratio = 0.3; 95% confidence interval = 0.127–0.749).

  • Resistance and Synergy: In vivo selection of bacteriophage resistance was observed in 43.8% of evaluated patients, while in vitro bacteriophage–antibiotic synergy was documented in 90% of evaluated patients.

  • Antibiotic Re-sensitization and Reduced Virulence: Bacteriophage-resistant bacterial isolates exhibited antibiotic re-sensitization and reduced virulence.

  • Immune Neutralization: Bacteriophage immune neutralization was observed in 38.5% of screened patients.

  • Adverse Events: The study reported 15 adverse events, including seven non-serious adverse drug reactions suspected to be linked to BT.

This analysis underscores the potential of personalized BT, particularly when used in combination with antibiotics, for treating difficult-to-treat infections. While limited by the uncontrolled nature of the data, the findings provide valuable insights for the design of future controlled clinical trials.

This study contributes to the growing body of evidence supporting personalized bacteriophage therapy as a promising avenue in addressing antibiotic-resistant infections.

Article DOI.

Exploring the Phageome: Differences in Healthy and Atopic Dermatitis Skin

Exploring the Phageome: Differences in Healthy and Atopic Dermatitis Skin

Exploring the Phageome: Differences in Healthy and Atopic Dermatitis Skin

Study workflow and bacterial communities in healthy skin and AD.

In this study published in Science Advances, Wolfgang Weninger and his team from the Medical University of Vienna, have highlighted the role of bacteriophages in the skin’s microbiome, particularly in relation to atopic dermatitis (AD).

By analyzing skin swabs from both healthy individuals and AD patients using shotgun metagenomics, the researchers identified over 13,000 potential viral DNA sequences. These sequences were combined into 164 putative viral genomes, 133 of which were identified as bacteriophages.

Interestingly, the study found that the diversity of these viral genomes, measured by the Shannon diversity index, did not correlate with the presence of AD. This suggests that the sheer variety of viruses isn’t the main factor in the disease’s progression. However, the research did uncover 28 viral genomes that significantly differed between healthy and AD-affected skin, indicating distinct viral communities in inflamed skin.

Moreover, the presence of these viral genomes was shown to be independent of the abundance of their bacterial hosts. This means that changes in the phageome aren’t just a byproduct of bacterial changes but may play a direct role in skin health and disease.

These findings suggest that shifts in the skin’s viral community could drive changes in bacterial populations, contributing to the development of AD. This opens up new possibilities for therapies that target both the viral and bacterial components of the skin microbiome.

Wolfgang Weninger will be discussing these insightful findings at the 7th World Conference Targeting Phage Therapy, taking place on June 20-21 in Malta. Learn more.

Article DOI.

Photo Credits: M. Wielscher et al. Sci. Adv. (2023)