Abstract
Gastrointestinal tract microbiota plays a key role in the regulation of the pathogenesis of several gastrointestinal diseases. In particular, the viral fraction, composed essentially of bacteriophages, influences homeostasis by exerting a selective pressure on the bacterial communities living in the tract. Gastrointestinal inflammatory diseases are mainly induced by bacteria, and have risen due to the emergence of antibiotic resistant strains. In the lack of effective treatments, phage therapy has been proposed as a clinical alternative to restore intestinal eubiosis, thanks to its immunomodulatory and bactericidal effect against bacterial pathogens, such as Clostridioides difficile in ulcerative colitis and invasive adherent Escherichia coli in Crohn’s disease. In addition, genetically modified temperate phages could be used to suppress the transcription of bacterial virulence factors. In this review, we will highlight the latest advances in research in the field, as well as the clinical trials based on phage therapy in the area of gastroenterology.
Highlights
The human body is hosting a challenging consortium of microorganisms comprising viruses, bacteria, archaea, fungi, and protozoa
By incorporating its genome into the bacterium, these temperate phages can induce a change in the phenotype of the host cell, providing advantages through gene transfer that improve host virulence and resistance to immune defenses, a process called lysogenic conversion
An interesting example of the use of genetically modified temperate phages was done to suppress the Shiga toxin (Stx) from an established E. coli population that colonizes the intestine of mammals, a pathogenic infection difficult to treat
Summary
The human body is hosting a challenging consortium of microorganisms comprising viruses, bacteria, archaea, fungi, and protozoa. By incorporating its genome into the bacterium, these temperate phages can induce a change in the phenotype of the host cell, providing advantages through gene transfer that improve host virulence and resistance to immune defenses, a process called lysogenic conversion. In addition to these classical cycles, chronic cycle and pseudolysogeny have been proposed as alternative pathways. Pseudolysogenesis is a stage in which the phage genome does not multiply (as in the lytic pathway), neither replicates in a synchronized and stable manner during the cell cycle (as in the lysogenic pathway), but remains within the host as an episome, independent from the host genome [5] After their discovery a century ago, phages have been used as therapeutic tools since the very beginning. The aim of this review is to analyze the latest scientific advances in phage therapy in the field of gastroenterology, highlighting its importance as a therapeutic tool [18]
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