Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, are chronic, relapsing intestinal inflammatory disorders. Although the molecular mechanisms governing the pathogenesis of IBD are not completely clear, the main factors are presumed to be a complex interaction between genetic predisposition, host immune response and environmental exposure, especially the intestinal microbiome. Currently, most studies have focused on the role of gut bacteria in the onset and development of IBD, whereas little attention has been paid to the enteroviruses. Among of them, viruses that infect prokaryotes, called bacteriophages (phages) occupy the majority (90%) in population. Moreover, several recent studies have reported the capability of regulating the bacterial population in the gut, and the direct and indirect influence on host immune response. The present review highlights the roles of gut phages in IBD pathogenesis and explores the potentiality of phages as a therapeutic target for IBD treatment.

Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches

“…Similarly, as in the bacteriome, there are highly specific interindividual differences in phage communities. The limited understanding of phage biology and the microbiological aspect of disease means that additional in vivo and in vitro studies are required to elucidate the roles of gut phages in IBD development and treatment [ 31 ].…”

"Out of the box� new therapeutic strategies for Crohn�s disease: moving beyond biologics

“…Bacteriophage richness was reported to be increased, whereas bacterial richness was reduced (129). Most studies have also showed elevated number but lower diversity of Caudovirales phages in UC and CD compared with healthy subjects (130).…”

“…In IBD, the phage composition -phageome-appears to be altered, but findings are inconsistent (129,130). Bacteriophage richness was reported to be increased, whereas bacterial richness was reduced (129).…”

Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota

“…Bacteriophages have been observed to induce phase variation in bacterial cells, leading to the switching 'OFF' of specific polysaccharides loci or increased expression of alternative polysaccharides with possible protective effects 30 . Moreover, they have been shown to be associated with intestinal inflammation and IBD in several studies 31,32 , including Nishiyama et al 33 who characterized temperate bacteriophages and their bacterial hosts in the IBDMDB metagenomics database. Here, using phage sequences from IBDMDB database, and compared the relative abundances of these phages between samples that displayed lower (<40%) or higher (>60%) ratios of the PSA promoter 'ON' orientation.…”