Viral Microbiome Changes Could Be an Underlying Cause of IBD

It’s relatively commonplace these days to associate the term microbiome only with bacterial communities. Yet, viruses infinitely outnumber bacteria, especially within the mammalian gut. As such, researchers at North Carolina State University, the University of Texas Southwestern Medical Center, and the University of Colorado wanted to know if the viral communities within the intestinal tract of mice influenced intestinal inflammation and disease. The scientists found some unexpected patterns and published their findings recently in Nature Microbiology through an article titled “Murine colitis reveals a disease-associated bacteriophage community.”

Studying the microbiome has become a major scientific focus in recent years, as researchers work to tease apart various interactions of microorganisms inside the gut to understand how they affect health. In the current study, the research team is hopeful that their results could lead to a better understanding of the potential causes and markers of inflammatory bowel disease (IBD).

The study authors wanted to learn more about bacteriophages and their potential role in intestinal inflammation. Bacteriophages are viruses that infect and often kill bacteria. Phage viruses vastly outnumber bacteria and thus have major effects on the trillions of bacteria living in the human intestinal tract. Using new quantitative metagenomics techniques specifically developed to better study viruses in the intestinal tract, the team of researchers compared the phage communities in healthy mice and mice with IBD.

“We used a sequence-independent approach for the selection of viral contigs and then applied quantitative metagenomics to study intestinal phages in a mouse model of colitis,” the authors wrote.

“We wanted to see how virus and bacterial communities differ in disease and healthy conditions,” adds co-lead study investigator Manuel Kleiner, Ph.D., assistant professor at NC State University.

Unsurprisingly, in healthy mice, bacterial and phage communities remained rather stable and comparable over time, which the researchers predicted. Generally, changes in the number of specific species of bacteria led to corresponding changes in the number of their viral predators.

However, diseased mice showed unexpected results. The viral communities in diseased mice over time became more diverse, not only from the healthy mice, which was expected but also between diseased mice. The number of bacteriophages that were detectable in diseased mice dropped enormously, and the remaining few bacteriophages became very abundant. Several of these bacteriophages are known to infect disease-causing bacteria, which also increased in abundance. However, some of the bacteriophages that became more dominant during inflammation were not linked to any of the disease-causing bacteria.

“We discovered that during colitis the intestinal phage population is altered and transitions from an ordered state to a stochastic dysbiosis,” the authors penned. “We identified phages specific to pathobiotic hosts associated with intestinal disease, whose abundances are altered during colitis. Additionally, phage populations in healthy and diseased mice overlapped with phages from healthy humans and humans with IBD.”

“Diseased mice showed individual divergent – seemingly random – increases in the abundance of some bacteriophages that are not associated with disease-causing bacteria. We speculate that inflammation or other mouse defenses may impact these bacteriophages,” Dr. Kleiner states.

The researchers compared these patterns to existing data and literature on healthy and diseased human microbial communities. Interestingly, and surprisingly, many of the patterns seen in healthy and diseased mice respectively overlapped with healthy and diseased viral communities seen in human populations.

“This was unexpected, as mouse studies are frequently viewed as limited when looking for links to human health, but we could show that there are consistent patterns in the viral community in inflammation in both mice and humans,” Dr. Kleiner concludes.