Are bacteriophages the culprit behind IBD?

Liz Meszaros, MDLinx | August 24, 2018

Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, may be linked to bacteriophages (phages)—viruses that inhabit bacteria—according to researchers who published their findings recently in Nature Microbiology.

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Bacteriophages that live within intestinal bacteria may be responsible for “ecological disturbances” that could be associated with inflammatory processes and the development of inflammatory bowel diseases.

Researchers led by Breck Duerkop, PhD, assistant professor of immunology and microbiology at the University of Colorado School of Medicine, Aurora, CO, undertook this study to find out if colitis changes the intestinal bacteriophage community. They used a murine model of T-cell adoptive transfer with chronic colon inflammation. Mice were injected with CD4+ CD45RBHigh T-cells or saline and monitored for weight loss and inflammatory markers. Using feces samples from the mice, the researchers isolated genomic DNA and virus-like particles (VLPs) and performed DNA sequencing.

They found an increased number of Proteobacteria at 42 days, a result that corroborated previous studies showing that Proteobacterial communities increase in the presence of intestinal inflammation. At day 0, samples from both T-cell–treated mice and controls had similar viral communities. By day 42, however, researchers observed a shift in the composition of these viral communities, which was characterized by a decrease in the abundance of viral contig (a set of overlapping DNA segments representing a region of DNA, or a read), and a significant loss of diversity. At this time, the differences between the T-cell–treated mice and healthy controls were characterized by increased dissimilarity.

“Phage numbers are elevated at the intestinal mucosal surface and increase in abundance during IBD, suggesting that phages play an unidentified role in IBD,” said Dr. Duerkop, who added that previous studies focused on bacteria rather than on the phages that live within them.

“We hypothesize that inflammation or other host defenses alter phage abundances during colitis. Such stresses could produce ecological disturbances in the intestinal environment, driving alterations within the viral community,” noted these authors.

These ”ecological disturbances” could be caused by the phages killing off beneficial bacteria, or perhaps allowing the ”bad” bacteria to proliferate, causing both inflammation and bowel disease.

Dr. Duerkop and colleagues suggested that future studies of how phages live and infect certain bacteria may lead to more targeting of therapeutic approaches for IBD. In addition, targeting bacteria that are infected with phages may help eliminate those that cause inflammation and IBDs.

“We hypothesize that inflammation or other host defenses alter phage abundances during colitis. Such stresses could produce ecological disturbances in the intestinal environment, driving alterations within the viral community,” concluded these authors. ” Our findings indicate that intestinal phage communities are altered during inflammatory disease, establishing a platform for investigating phage involvement in IBD.”

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