A Closer Look Into Viral Dark Matter

Taking a metagenomics approach, researchers in Japan have identified phage-derived enzymes that could potentially treat an imbalance of gut bacteria.

AsianScientist (Aug. 11, 2020) – A study of over a hundred Japanese volunteers has revealed the complex interactions between bacteria and viruses in the gut. The team behind this study, from Osaka City University and the University of Tokyo, have published their findings in Cell Host & Microbe.

The human gut plays host to between 200 to 500 different species of bacteria, as well as viruses that target bacteria known as bacteriophages. When the delicate balance between these gut residents is upset—as can occur after antibiotic use or certain diseases—the result is dysbiosis.

Altered microbial diversity blunts the beneficial effects of healthy intestinal microflora, and can cause some symbiotic commensal bacteria to acquire virulence traits, proliferate and become directly involved in the development of disease. These bacteria are referred to as ‘pathobionts,’ and are distinct from opportunistic pathogens.

One approach to controlling pathobionts is to use bacteriophages targeting specific species. However, the precise interactions between phages and bacteria in the human intestine are so poorly understood that they are sometimes referred to as “viral dark matter.”

To better understand the diversity of both bacteria and bacteriophages in the gut, a team led by Professor Satoshi Uematsu of Osaka City University, Japan, sequenced the bacterial and viral metagenomes in stool samples from 101 healthy individuals. Using a virome analysis pipeline they developed, the researchers focused on phages specific to Clostriditum difficile, a Gram-positive, spore-forming anaerobic bacterium that can cause diarrhea following antibiotic treatment.

Their analysis identified phage-derived antibacterial enzymes that can control pathobionts like C. difficile. To demonstrate that phages can be used to eliminate pathobionts, the team conducted a proof-of-concept study, showing that the phage-derived enzymes were able to regulate C. difficile infections in mice.

“The accumulation of more metagenomic information on intestinal phages and bacteria will open up the possibility of developing treatments for a variety of dysbiosis-related diseases,” said study first author Dr. Kosuke Fujimoto of the University of Tokyo, Japan.

The article can be found at: Fujimoto et al. (2020) Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts.


Source: Osaka City University; Photo: Shutterstock.
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