Delivering phage therapy <i>per os</i>: benefits and barriers

Zelasko, Susan; Górski, Andrzej; Dąbrowska, Krystyna

doi:10.1080/14787210.2017.1265447

Cited by 24 publications

(17 citation statements)

References 117 publications

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“…Phage treatment for gastrointestinal diseases by oral administration has been studied for a long time. Due to sensitivity to acidic compounds, digestive enzymes, and mucus layer containing IgA antibodies in the gastrointestinal tract, most phages showed limited effect during oral application (Zelasko et al, 2017). The stability of phages under various conditions is an important factor in evaluating their bactericidal potential.…”

Section: Discussionmentioning

confidence: 99%

The Yersinia Phage X1 Administered Orally Efficiently Protects a Murine Chronic Enteritis Model Against Yersinia enterocolitica Infection

et al. 2020

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Yersinia enterocolitica is generally considered an important food-borne pathogen worldwide, especially in the European Union. A lytic Yersinia phage X1 (Viruses; dsDNA viruses, no RNA stage; Caudovirales; and Myoviridae) was isolated. Phage X1 showed a broad host range and could effectively lyse 27/51 Y. enterocolitica strains covering various serotypes that cause yersiniosis in humans and animals (such as serotype O3 and serotype O8). The genome of this phage was sequenced and analyzed. No toxin, antibiotic-resistance or lysogeny related modules were found in the genome of phage X1. Studies of phage stability confirmed that X1 had a high tolerance toward a broad range of temperatures (4-60 • C) and pH values (4-11) for 1 h. The ability to resist harsh acidic conditions and enzymatic degradation in vitro demonstrated that phage X1 is suitable for oral administration, and in particular, that this phage can pass the stomach barrier and efficiently reach the intestine in vivo without losing infectious ability. The potential of this phage against Y. enterocolitica infection in vitro was studied. In animal experiments, a single oral administration of phage X1 at 6 h post infection was sufficient to eliminate Y. enterocolitica in 33.3% of mice (15/45). In addition, the number of Y. enterocolitica strains in the mice was also dramatically reduced to approximately 10 3 CFU/g after 18 h compared with 10 7 CFU/g in the mice without phage treatment. Treatment with phage X1 showed significant improvement by intestinal histopathologic observations. Moreover, proinflammatory cytokine levels (IL-6, TNF-α, and IL-1β) were significantly reduced (P < 0.05). These results indicate that phage X1 is a promising candidate to control infection by Y. enterocolitica in vivo.

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Section: Discussionmentioning

confidence: 99%

The Yersinia Phage X1 Administered Orally Efficiently Protects a Murine Chronic Enteritis Model Against Yersinia enterocolitica Infection

et al. 2020

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“…It may be used both as a local application for treatment of intestinal infections as well as a systemic administration for treatment of diseases located outside of the digestive tract (Zelasko et al, 2017). However, the data confirming the possibility of the phage transit through gastrointestinal mucosa in humans are scarce (Weber-Dąbrowska et al, 1987; Pagava et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Means to Facilitate the Overcoming of Gastric Juice Barrier by a Therapeutic Staphylococcal Bacteriophage A5/80

et al. 2017

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In this article we compare the efficacy of different pharmacological agents (ranitidine, and omeprazole) to support phage transit from stomach to distal portions of the gastrointestinal tract in rats. We show that a temporal modification of environment in the animal stomach may protect Twort-like therapeutic antistaphylococcal phage A5/80 (from bacteriophage collection of the Hirszfeld Institute of Immunology and Experimental Therapy PAS in Wroclaw, Poland) from the inactivation by gastric juice effectively enough to enable a significant fraction of orally administered A5/80 to pass to the intestine. Interestingly, we found that yogurt may be a relatively strong in enhancing phage transit. Given the immunomodulating activities of phages our data may suggest that phages and yogurt can act synergistically in mediating their probiotic activities and enhancing the effectiveness of oral phage therapy. We also demonstrate that orally applied phages of similar size, morphology, and sensitivity to acidic environment may differ in their translocation into the bloodstream. This was evident in mice in which a therapeutic staphylococcal phage A5/80 reached the blood upon oral administration combined with antacid agent whilst T4 phage was not detected even when applied in 103 times higher dose. Our findings also suggest that phage penetration from digestive tract to the blood may be species-specific.

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“…It remains relatively unknown which factors or characteristics allow for a phage to possess a degree of acid resistance. The acidic pH-level of the stomach is a main concern for all orally applied phage formulations and can be addressed by embedding the phage in acid resistant polymer matrices (Zelasko et al, 2017).…”

Section: Considerations In Manufacturing Bacteriophage Loaded Biomatementioning

confidence: 99%

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

et al. 2020

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As viruses with high specificity for their bacterial hosts, bacteriophages (phages) are an attractive means to eradicate bacteria, and their potential has been recognized by a broad range of industries. Against a background of increasing rates of antibiotic resistance in pathogenic bacteria, bacteriophages have received much attention as a possible "last-resort" strategy to treat infections. The use of bacteriophages in human patients is limited by their sensitivity to acidic pH, enzymatic attack and short serum half-life. Loading phage within a biomaterial can shield the incorporated phage against many of these harmful environmental factors, and in addition, provide controlled release for prolonged therapeutic activity. In this review, we assess the different classes of biomaterials (i.e., biopolymers, synthetic polymers, and ceramics) that have been used for phage delivery and describe the processing methodologies that are compatible with phage embedding or encapsulation. We also elaborate on the clinical or preclinical data generated using these materials. While a primary focus is placed on the application of phage-loaded materials for treatment of infection, we also include studies from other translatable fields such as food preservation and animal husbandry. Finally, we summarize trends in the literature and identify current barriers that currently prevent clinical application of phage-loaded biomaterials.

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Delivering phage therapy per os: benefits and barriers

Cited by 24 publications

References 117 publications

The Yersinia Phage X1 Administered Orally Efficiently Protects a Murine Chronic Enteritis Model Against Yersinia enterocolitica Infection

The Yersinia Phage X1 Administered Orally Efficiently Protects a Murine Chronic Enteritis Model Against Yersinia enterocolitica Infection

Means to Facilitate the Overcoming of Gastric Juice Barrier by a Therapeutic Staphylococcal Bacteriophage A5/80

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

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