Abstract

Increased intestinal permeability and translocation of gut bacteria trigger various polyaetiological diseases associated with chronic inflammation and underlie a variety of poorly treatable pathologies. Previous studies have established a primary role of the microbiota composition and intestinal permeability in such pathologies. Using a rat model, we examined the effects of exposure to a bacteriophage cocktail on intestinal permeability and relative abundance of taxonomic units in the gut bacterial community. There was an increase in markers of impaired gut permeability, such as the lactulose/mannitol ratio, plasma endotoxin concentrations, and serum levels of inflammation-related cytokines, following the bacteriophage challenge. We observed significant differences in the alpha diversity of faecal bacterial species and found that richness and diversity index values increased following the bacteriophage challenge. There was a reduction in the abundance of Blautia, Catenibacterium, Lactobacillus, and Faecalibacterium species and an increase in Butyrivibrio, Oscillospira and Ruminococcus after bacteriophage administration. These findings provide novel insights into the role of bacteriophages as potentially pathogenic for mammals and their possible implication in the development of diseases associated with increased intestinal permeability.

Highlights

  • Our knowledge of the intestinal microbiota has greatly expanded over the last decade, and growing evidence suggests that alterations of the intestinal microbiota are critical pathogenic factors that trigger various polyaetiological diseases associated with increased intestinal permeability and chronic inflammation[1,2,3]

  • All animals showed unkempt hair coats and decreased activity starting from the 5th day of bacteriophage administration, which we believe was due to the induction of endotoxemia and impaired intestinal permeability[16]

  • With the impaired gut permeability, bacterial antigens cross into the lamina propria, leading to endotoxemia and dysregulation of inflammatory responses, and trigger chronic inflammation, which in turn is an important factor for the development of various polyaetiological diseases[20, 21]

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Summary

Introduction

Our knowledge of the intestinal microbiota has greatly expanded over the last decade, and growing evidence suggests that alterations of the intestinal microbiota are critical pathogenic factors that trigger various polyaetiological diseases associated with increased intestinal permeability and chronic inflammation[1,2,3]. We have previously reported that the challenge with bacteriophages is associated with altered intestinal permeability; some questions remained unanswered, in particular how microbial composition of the gut microbiota changes and whether it correlates with the increased intestinal permeability and endotoxemia To investigate these issues, we carried out Illumina sequencing of the V3–V4 region of the 16S ribosomal RNA (rRNA) gene to compare the microbiota composition before and after a bacteriophage challenge and to uncover its role in the increased intestinal permeability and endotoxemia in rats[15]. We carried out Illumina sequencing of the V3–V4 region of the 16S ribosomal RNA (rRNA) gene to compare the microbiota composition before and after a bacteriophage challenge and to uncover its role in the increased intestinal permeability and endotoxemia in rats[15] This information can provide a basis for the crucial step in the evaluation of bacteriophage implications in poorly treatable human diseases

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