Therapeutic Phages as Modulators of the Immune Response: Practical Implications

Górski, Andrzej; Międzybrodzki, Ryszard; Jończyk-Matysiak, Ewa; Kniotek, Monika; Letkiewicz, Sławomir

doi:10.1093/cid/ciad483

Cited by 5 publications

(2 citation statements)

References 68 publications

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“…Indeed, oral administration of high-titer phages in mouse studies has shown translocation into blood and tissue, 54 even in the absence of disease. 55 As phages have the potential to elicit context-dependent inflammatory, and anti-inflammatory responses in systemic circulation, 29–31 , 56 physiologically relevant models to understand gastrointestinal phage translocation are sorely needed. To study phage translocation in the colon and define factors that enhance and prevent their migration, we have generated an ex vivo colon-derived monolayer model, based on previous works by In et al.…”

Section: Discussionmentioning

confidence: 99%

Using a human colonoid-derived monolayer to study bacteriophage translocation

Le,

Lubian,

Bowring

et al. 2024

Gut Microbes

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Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo , we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo . We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.

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Section: Discussionmentioning

confidence: 99%

Using a human colonoid-derived monolayer to study bacteriophage translocation

Le,

Lubian,

Bowring

et al. 2024

Gut Microbes

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“…Interestingly, recent studies suggest that phage can also influence microbiome compositions, interact with eukaryotic cells, and modulate immune responses. 101 Yet, the impact of phage therapy in treating chronic wound infection and modulating local immune responses to promote healing is under‐investigated.…”

Section: Current Treatments Against Chronic Infectionsmentioning

confidence: 99%

Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies

Norton,

Trus,

Wang

et al. 2024

Skin Health and Disease

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BackgroundNotoriously known as the silent pandemic, chronic, non‐healing diabetic foot ulcers (DFUs), pose a significant rate of incidence for amputation and are a major cause of morbidity. Alarmingly, the treatment and management strategies of chronic wounds represent a significant economic and health burden as well as a momentous drain on resources with billions per annum being spent in the US and UK alone. Defective wound healing is a major pathophysiological condition which propagates an acute wound to a chronic wound, further propelled by underlying conditions such as diabetes and vascular complications which are more prevalent amongst the elderly. Chronic wounds are prone to infection, which can exacerbate the condition, occasionally resulting in amputation for the patient, despite the intervention of modern therapies. However, amputation can only yield a 5‐year survival rate for 50% of patients, highlighting the need for new treatments for chronic wounds.FindingsThe dynamic cutaneous microbiota is comprised of diverse microorganisms that often aid wound healing. Conversely, the chronic wound microbiome consists of a combination of common skin commensals such as Staphylococcus aureus and Staphylococcus epidermidis, as well as the opportunistic pathogen Pseudomonas aeruginosa. These bacteria have been identified as the most prevalent bacterial pathogens isolated from chronic wounds and contribute to prolific biofilm formation decreasing the efficiency of antimicrobials and further perpetuating a hyper‐inflammatory state.Discussion and ConclusionHere, we review recent advances and provide a new perspective on alternative treatments including phage and microbiome transplant therapies and how the definitive role of the cutaneous microbiota impacts the aetiology of DFUs.

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Characterization of Newly Isolated Bacteriophages Targeting Carbapenem-Resistant Klebsiella pneumoniae

Kim,

Choi

et al. 2024

J Microbiol.

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Therapeutic Phages as Modulators of the Immune Response: Practical Implications

Cited by 5 publications

References 68 publications

Using a human colonoid-derived monolayer to study bacteriophage translocation

Using a human colonoid-derived monolayer to study bacteriophage translocation

Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies

Characterization of Newly Isolated Bacteriophages Targeting Carbapenem-Resistant Klebsiella pneumoniae

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