Just a phage? How predators of bacteria can shape the intestinal microbiome

The intestinal microbiome is a complex ecosystem of interconnected species. And, like any ecosystem, some organisms are predators and others prey. A new study by investigators from Brigham and Women's Hospital and the Wyss Institute is investigating the impact of bacteriophage, a virus that infects and destroys bacteria. They find that phage can have a profound impact on the dynamics of the intestinal microbiome, not only directly affecting certain species, but also having a cascading effect on others. Phage can also impact their human host by modulating their metabolites, including chemicals in the brain. The team, which includes the first author Bryan Hsu, Ph.D., and corresponding lead author, Pamela Silver, Ph.D., at the Wyss Institute, and Lynn Bry, MD, Ph.D., from Brigham and Massachusetts Host-Microbiome Center director, published his findings in Cell Host & Microbe.

"One of the main interests of my laboratory is to understand the changes in the dynamics of the intestinal microbiome.Bacteriophages are an important component of the microbiome but have not yet been studied extensively," said the principal author Partner, Georg Gerber, MD. Ph.D., MPH, co-director of the Massachusetts Host-Microbiome Center and Head of the Computational Pathology Division of the Brigham Department of Pathology. "Some people are exploring phage therapy, using phages to kill microbes, but phages are also found naturally in the intestines, coexisting with the rest of the ecosystem." We wanted to know what they were doing there . "

To answer this question, the team colonized the entrails of mice with a defined set of human bacterial species, and then added phages, following the growth of each microbe. Using sequencing and high throughput analysis, the team found that the phage was causing wear and tear on the species they were prey to as expected, but with an effect training on the rest of the ecosystem, including the proliferation of non-targeted species.

In addition to examining the effects on microbes, the team also looked for effects on the metabolome, chemicals that can come from both the host and the bacteria present. They found that when they modulated the microbiome with phage, they could observe targeted changes in the metabolome, including changes in neurotransmitter levels and bile acids.

"This discovery fascinates me for follow-up and raises important questions: could we use a phage to modulate these activities, or would it be an intervention for conditions, such as depression, where you would like to change neurotransmitter levels?" Gerber said. "Even though they are not used as direct treatment, our study suggests that phage could be a good tool for understanding the potential effects of other treatments that alter the microbiome."

Gerber and his colleagues are particularly interested in the intersection of phage and malnutrition in developing countries, given the profound effects that malnutrition can have on the metabolome and the microbiome.

"We hope that our work will provide a framework to guide future research to elucidate the interaction between phage, microbiota and health and host disease," he said. Gerber said.