Carrier systems for bacteriophages to supplement food systems: Encapsulation and controlled release to modulate the human gut microbiota

Orally administered phages to control zoonotic pathogens face important challenges, mainly related to the hostile conditions found in the gastrointestinal tract (GIT). These include temperature, salinity and primarily pH, which is exceptionally low in certain compartments. Phage survival under these conditions can be jeopardized and undermine treatment. Strategies like encapsulation have been attempted with relative success, but are typically complex and require several optimization steps. Here we report a simple and efficient alternative, consisting in the genetic engineering of phages to display lipids on their surfaces. Escherichia coli phage T7 was used as a model and the E. coli PhoE signal peptide was genetically fused to its major capsid protein (10 A), enabling phospholipid attachment to the phage capsid. The presence of phospholipids on the mutant phages was confirmed by High Performance Thin Layer Chromatography, Dynamic Light Scattering and phospholipase assays. The stability of phages was analysed in simulated GIT conditions, demonstrating improved stability of the mutant phages with survival rates 102–107 pfu.mL−1 higher than wild-type phages. Our work demonstrates that phage engineering can be a good strategy to improve phage tolerance to GIT conditions, having promising application for oral administration in veterinary medicine.

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“…for phage CA933P, Ma et al 32. for phage Felix O1, and Samtlebe et al 31. for phage P008, using encapsulation methods.…”

Section: Resultsmentioning

confidence: 99%

“…Phage encapsulation in natural biopolymer-derived matrices have been used as a strategy to improve phage stability2728293031. An increased survival of phages has been obtained with this technology in the GIT of cattle, pigs and poultry273233.…”

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confidence: 99%

Genetically manipulated phages with improved pH resistance for oral administration in veterinary medicine

Nóbrega

Costa

Santos

et al. 2016

Sci Rep

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“…Alginate is one of the most common biomaterials used in microencapsulation, including that of probiotics1415 and, as recently shown, bacteriophages. The latter was achieved using alginate either alone or in combination with other components, in which wet capsules ranging in size from 310 μm to almost 1 mm were obtained810161718. Alginate, a linear copolymer containing blocks of (1, 4)-linked β-D-mannuronate and α-L-guluronate residues, is of low toxicity and immunogenicity and thus regarded as a biocompatible material19.…”

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confidence: 99%

Microencapsulation with alginate/CaCO3: A strategy for improved phage therapy

Colom

Cano‐Sarabia

Otero

et al. 2017

Sci Rep

132

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Bacteriophages are promising therapeutic agents that can be applied to different stages of the commercial food chain. In this sense, bacteriophages can be orally administered to farm animals to protect them against intestinal pathogens. However, the low pH of the stomach, the activities of bile and intestinal tract enzymes limit the efficacy of the phages. This study demonstrates the utility of an alginate/CaCO3 encapsulation method suitable for bacteriophages with different morphologies and to yield encapsulation efficacies of ~100%. For the first time, a cocktail of three alginate/CaCO3-encapsulated bacteriophages was administered as oral therapy to commercial broilers infected with Salmonella under farm-like conditions. Encapsulation protects the bacteriophages against their destruction by the gastric juice. Phage release from capsules incubated in simulated intestinal fluid was also demonstrated, whereas encapsulation ensured sufficient intestinal retention of the phages. Moreover, the small size of the capsules (125–150 μm) enables their use in oral therapy and other applications in phage therapy. This study evidenced that a cocktail of the three alginate/CaCO3-encapsulated bacteriophages had a greater and more durable efficacy than a cocktail of the corresponding non-encapsulated phages in as therapy in broilers against Salmonella, one of the most common foodborne pathogen.

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“…This modular construction of synthetic bacteriophages allows for very specific targeting of a very broad array of different bacteria. Moreover, novel delivery systems permit bacteriophages to be administered as food supplements, improving localization and impact of the treatment [123]. Combining these technologies may provide a method to selectively eliminate individual detrimental members of a microbiota as a way to fight dysbiosis and disease.…”

Section: Figure Imentioning

confidence: 99%

Emerging Technologies for Gut Microbiome Research

Arnold

Roach

Azcárate-Peril

2016

Trends in Microbiology

167

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Understanding the importance of the gut microbiome on modulation of host health has become a subject of great interest for researchers across disciplines. As an intrinsically multidisciplinary field, microbiome research has been able to reap the benefits of technological advancements in systems and synthetic biology, biomaterials engineering, and traditional microbiology. Gut microbiome research has been revolutionized by high-throughput sequencing technology, permitting compositional and functional analyses that were previously an unrealistic undertaking. Emerging technologies including engineered organoids derived from human stem cells, high-throughput culturing, and microfluidics assays allowing for the introduction of novel approaches will improve the efficiency and quality of microbiome research. Here, we will discuss emerging technologies and their potential impact on gut microbiome studies.

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Carrier systems for bacteriophages to supplement food systems: Encapsulation and controlled release to modulate the human gut microbiota

Cited by 34 publications

References 43 publications

Genetically manipulated phages with improved pH resistance for oral administration in veterinary medicine

Genetically manipulated phages with improved pH resistance for oral administration in veterinary medicine

Microencapsulation with alginate/CaCO3: A strategy for improved phage therapy

Emerging Technologies for Gut Microbiome Research

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