Phages and Their Role in Gastrointestinal Disease: Focus on Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBDs) are a group of chronic autoinflammatory diseases including Crohn’s disease and ulcerative colitis. Although the molecular mechanisms governing the pathogenesis of gastrointestinal inflammation are not completely clear, the main factors are presumed to be genetic predisposition, environmental exposure, and the intestinal microbiome. Hitherto, most of the studies focusing on the role of the microbiome studied the action and effect of bacteria. However, the intestinal microbiome comprises other members of the microbial community as well, namely, fungi, protozoa, and viruses. We believe that bacteriophages are among the main orchestrators of the effect of microbiota on the gut mucosa. Therefore, this review aims to summarize the knowledge of the role of intestinal phageome in IBD and to discuss the concept of phage therapy and its future applications.

Metagenomic analysis of primary colorectal carcinomas and their metastases identifies potential microbial risk factors

“…The phage-mediated bacteriolysis might induce a wave of endotoxins able to ignite the immune response, albeit its extent is not completely understood. Nevertheless, it has been hypothesized that such stimulation might be involved in establishing chronic inflammation [128][129][130][131].Tetz and Tetz [30] are the principal advocates of the possible pathogenic consequences of phage activity, andgiven the preliminary state of research on phage interaction with human physiology, it is not surprising that there is little literature besides the one cited of these two authors. Moreover, most of the descriptions of phage immunity have been rather inferred than clinically demonstrated.…”

Phage Therapy in Gastrointestinal Diseases

“…Phages are a promising alternative to modulate the intestinal microbiota by eliminating pathogenic bacteria. Currently, lytic phage therapy is mainly being explored in gastroenterology to combat C. difficile UC and the eradication of AIEC in CD [ 17 ]. The most important issue for the therapeutic development of phages is to evaluate the safety and efficacy of the phages to be used.…”

“…The current situation requires the urgent implementation of new therapeutic strategies against infectious diseases, which has brought phage therapy as an interesting alternative. In gastroenterology, phages have been principally explored as promising tools in infectious diseases including cholera, and it is being tested against Clostridioides difficile colitis, and the eradication of adherent invasive Escherichia coli (AIEC) in CD [ 16 , 17 ]. 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 ].…”

Genome binning of viral entities from bulk metagenomics data

“…In IBD, multiple studies have compiled a list of keystone bacterial species undergoing microbial shifts between inflamed and non-inflamed tissue sites 4,5 and there are strong indications that the gut virome plays a role in disease etiology [6][7][8] . Now, the influence of bacteria-infecting viruses, known as bacteriophages, are increasingly studied and their role in controlling bacterial community dynamics in the context of gastrointestinal pathologies is slowly being unravelled 9 . Several studies have presented evidence of temperate Caudovirales viruses increasing in Crohn's disease (CD) and ulcerative colitis (UC) patients 6,8,[10][11][12] .…”