Personalised phage therapy is a therapeutic approach that involves using tailored bacteriophages to target and eliminate specific, harmful bacterial infections in a patient. This therapy is currently being explored as a potential alternative to antibiotics, particularly in cases where antibiotic resistance is a concern. Nexabiome is a Glasgow-based biotech company whose phage experts are interested in developing bacteriophages to target specific bacterial problems. The scientists at Nexabiome work to identify, isolate, and supply bespoke phage cocktails for various applications, including personalised phage therapy.
Bacteriophages, commonly known as phages, are viruses that selectively target and kill specific bacteria. A Lytic phage infects a bacterial cell, injecting its genetic material. The phage then replicates by hijacking the host’s cellular replication machinery. Eventually, this causes the host cell to rupture (undergo lysis), releasing the newly formed phages into the surrounding environment where they can infect neighbouring cells, continuing the cycle.
Phage genomes contain RNA or DNA, which can be single- or double-stranded, packed into a capsid. Bacteriophages are highly diverse, and each species has a specific host range, meaning they are only capable of infecting a precise bacterial species.
Phages can be applied to a broad range of applications, spanning healthcare, agriculture, aquaculture, and more. For infection treatment, the specificity of phages is advantageous over antibiotics, as it narrows the potential for resistance development (though phage resistance is still possible) and minimises damage to the microbiota, a common side effect of antibiotics. Antibiotics are not as specific, and some are bacteriostatic; both of these features encourage resistance, which is highly undesirable in the current antimicrobial resistance (AMR) crisis.
Personalised Phage Therapy
Personalised phage therapy uses bacteriophages to target and eliminate bacterial infections. The therapy is personalised because the specific phages used are tailored to the individual patient’s infection, as determined through bacterial culture and genetic analysis. The phages are produced in a laboratory and administered to the patient, either orally or intravenously.
The high host specificity of phages means that personalised phage therapy can be highly targeted, only damaging the target bacteria (those causing the infection) and leaving the body’s beneficial bacteria (i.e. the gut microbiome) unscathed. Phages can evolve and adapt, and bacteria are much less likely to become resistant to phages, making them a good candidate to treat antibiotic-resistant infections. Practically, phages’ are non-toxic and their inherent ability to replicate provides natural “auto-dosing” properties, meaning low doses are required.
Potential limitations and challenges of personalised phage therapy include the need for accurate bacterial identification and matching with the appropriate phages, which can be time-consuming and expensive, despite the relatively quick and cheap discovery process for phages themselves. Additionally, regulatory approval and manufacturing of personalised phage therapy can be complex and require significant resources.
The Role of the Microbiome in Personalised Phage Therapy
The microbiome refers to the population of microorganisms, including bacteria, viruses, fungi, and other microbes, that live on and within the human body. These microorganisms are essential for various physiological processes and contribute to overall health. The microbiome consists of both symbiotic (beneficial) and smaller numbers of pathogenic (potentially harmful) microbes. Symbiotic and pathogenic microbes coexist and interact within the network of microbiota. However, disruption to the balance of beneficial: harmful microbes perturbs these interactions, a process known as dysbiosis. Dysbiosis can be caused by infections, diet, or prolonged antibiotic use, and it increases the body’s susceptibility to infectious diseases.
The microbiome can influence infection treatment in several ways, including by the production of antimicrobial substances, competition with pathogenic bacteria for resources and attachment sites, and modulation of the immune response. Changes in the microbiome can affect the efficacy of antibiotics and other medicines. The gut microbiome can impact the composition of bacterial communities and their susceptibility to phage infection, as well as the ability of phages to colonise the gut. Therefore, consideration of the gut microbiome in the selection and administration of phages can improve the success and safety of personalised phage therapy. Additionally, understanding the interactions between phages and the gut microbiome can help inform the development of new phage-based therapies.
Personalised Phage Therapy in Action
Personalised phage therapies remain in their early stages and are yet to be fully adopted as antibiotic alternatives to treat bacterial infections. However, some examples highlight successful infection treatment with personalised phage therapy. A Frontiers publication reported that personalised phage therapy, used in combination with other medicines, successfully treated an antibiotic-resistant hospital-acquired pneumonia infection in a patient with chronic obstructive pulmonary disease (COPD). The treatment was well tolerated and led to the clearance of the infection and improved lung function. A recent report in Nature Communications highlighted the successful recovery of a patient with a pan-drug-resistant spinal abscess, following treatment with a personalised phage cocktail.
These examples, amongst others, highlight the usefulness of personalised phage therapy in treating infections, particularly infections that may otherwise be very difficult to treat. The upward trend in studies reporting the successful use of personalised phage therapy is promising. Now it is clear that the AMR crisis is here to stay, governments are developing programmes to improve our understanding of AMR and organisations are beginning to develop phage therapy infrastructures. Nonetheless, the lack of evidence regarding the safety and efficacy of personalised phage therapy, which is attributed to its personalised nature making it unsuitable for large-scale randomised clinical trials, continues to pose challenges. Moreover, to promote the wider adoption of phage therapy in precision medicine, addressing technical challenges and cost concerns associated with developing tailored phage cocktails is essential.
Conclusions and Future Perspectives
Personalised phage therapy presents a promising alternative to traditional antibiotics, offering a targeted approach that can overcome antibiotic resistance and minimise collateral damage to the gut microbiome. The potential of personalised phage therapy in healthcare is vast, with several successful case studies demonstrating its effectiveness in treating otherwise difficult-to-treat infections. The inherent non-toxicity, adaptability, and specificity of phages offer significant advantages over antibiotics, and can potentially revolutionise the treatment of bacterial infections. Despite its potential, personalised phage therapy still faces limitations and challenges, including the need for accurate bacterial identification, complex regulatory approvals, and resource-intensive manufacturing processes. To fully realise the benefits of this novel treatment approach, it is crucial to continue researching and refining the therapy, addressing these challenges, and exploring the complex interactions between phages and the gut microbiome. To learn more about the vast range of applications of phage, check out our other blogs.