Viruses found in the gut (collectively known as the gut virome) activate the immune system and help metabolize carbohydrates, thereby reducing blood sugar spikes, a new study in mice shows.
The findings, published March 11 in the journal Cell Host & Microbe, suggest that the virome may be involved in metabolic diseases such as diabetes, the study authors said.
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Barr added that this new discovery lays the foundation for future virus-based treatments for diseases associated with changes in the microbial community present in the gut.
Trillions of viruses breed on and within various organs, including the intestines, lungs, liver, kidneys, and brain. Most viruses in the gut are bacteriophages, which infect bacteria and influence their growth, forming a larger gut microbial ecosystem.
Previous studies have shown that intestinal bacteriophage composition is altered in metabolic disorders such as obesity, nonalcoholic fatty liver disease, and type 2 diabetes. This led Aikun Hu, a microbiologist at China’s Zhejiang University, and his team to speculate that viruses that infect bacteria can affect the body’s nutrient absorption and digestion processes, which are closely related to metabolic health.
To test their hypothesis, the authors disrupted the mice’s intestinal virome using an antiviral cocktail that primarily reduced bacteriophage levels and fed the mice either a carbohydrate-rich or fat-rich diet for 25 days. The disrupted intestinal virome had no appreciable effect on the digestion and absorption of nutrients in the animals fed the high-fat diet. However, mice that ate a high-carbohydrate diet had impaired glucose tolerance, despite increased expression of genes related to carbohydrate digestion and absorption. The intestines of these animals quickly broke down carbohydrates, causing a rapid rise in blood sugar levels, a hallmark of diabetes.
The fact that the virome can directly stimulate and activate carbohydrate metabolism, a fundamental energy intake and storage pathway, is completely novel.
Jeremy Barr, virologist at Monash University
The antiviral cocktail did not affect the diversity or function of gut bacteria, indicating that the effects of a disrupted virome are independent of gut bacteria.
In a separate experiment, the researchers enriched the viral load in the guts of infertile mice with no microbiome, either by transplanting the virus from the feces of another mouse or by injecting bacteriophages directly into the intestines. In both cases, the mice showed improved glucose tolerance and decreased expression of carbohydrate digestion and absorption genes.
To understand how bacteriophages caused these metabolic changes, Fu and his team introduced fluorescent virus-like particles (replication-incompetent viral proteins) into the intestines of mice and observed that the viruses were taken up by T cells, a subset of immune cells. Follow-up analysis showed that the virome stimulates the immune system to release proteins that prevent excess glucose from being carried into the bloodstream. Without phages, this immune response is blunted and more sugar quickly enters the bloodstream.
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The researchers repeated the experiment using human small intestine organoids, smaller versions of the organ grown from stem cells in the lab. Human enteric virus was present. They observed similar relationships between the virome, immune system, and carbohydrate metabolism.
“The fact that the virome can directly stimulate and activate carbohydrate metabolism, a fundamental energy intake and storage pathway, is completely novel,” Barr said.
Colin Morris, a microbiologist at McGill University who was not involved in the study, said the study also suggests that researchers need to think about viruses when considering gut health. “They show that there is an interaction between the virome and the immune system that we didn’t realize until now,” Morris told Live Science.
Although the findings highlight the importance of viruses in carbohydrate metabolism, researchers do not know how different types of viruses affect this process.
Now, Fu hopes to develop drugs and other strategies to change the virome and, by extension, diseases such as diabetes. However, the experts stressed that much research is still needed to understand how the human gut virome behaves in different disease states before potential treatments can be developed.
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