Viruses in the gut may help prevent blood sugar spikes, mouse study hints
Viruses in the intestines – collectively called the gut virome – activate the immune system to help metabolize carbohydrates, thereby reducing blood sugar spikes, according to a new study in mice.
The results, published March 11 in the journal Cellular host and microbesuggest that the virome may play a role in metabolic disorders such as diabetes, the study authors said.
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New discoveries lay the foundation for the future virus-based therapies for diseases associated with changes in the community of microorganisms that exist inside the intestine, Barr added.
Billions of viruses grow on and in different organsincluding the intestine, lungs, liver, kidneys and brain. Most viruses present in the intestine are bacteriophagesthat infect bacteria and influence their growth, thereby shaping the larger intestinal microbial ecosystem.
Previous work has shown that modification of the composition of intestinal bacteriophages in cases of metabolic disorders like obesity, non-alcoholic fatty liver disease and type 2 diabetes. This prompted Aikun Fumicrobiologist at Zhejiang University in China, and his team to speculate that viruses that infect bacteria might influence how the body absorbs and digests nutrients – processes closely linked to metabolic health.
To test their hypothesis, the authors disrupted mouse gut viromes, using an antiviral cocktail that primarily reduced bacteriophage levels, and fed the mice either a high-carbohydrate or high-fat diet for 25 days. A disrupted gut virome had no noticeable effect on digestion and nutrient absorption in animals fed a high-fat diet. But mice that ate a high-carbohydrate diet had impaired sugar tolerance, even though they increased the expression of genes related to carbohydrate digestion and absorption. The intestines of these animals quickly break down carbohydrates, leading to a sharp rise in blood sugar levels, a characteristic of diabetes.
The fact that the virome can directly stimulate and activate carbohydrate metabolism, a fundamental pathway for energy absorption and conservation, is completely new,
Jeremy Barr, virologist at Monash University
The antiviral cocktail did not affect the diversity or function of gut bacteria, indicating that the effects of the disrupted virome were independent of gut bacteria.
In a separate experiment, the team enriched the gut viral load in sterile mice lacking a microbiome, either by transplanting viruses from another mouse’s stool or by directly injecting bacteriophages into the gut. In both cases, the mice showed improved glucose tolerance and reduced expression of carbohydrate digestion and absorption genes.
To understand how bacteriophages caused these metabolic changes, Fu and his team introduced fluorescent virus-like particles – viral proteins with no ability to replicate – into the intestines of mice and observed that the viruses were taken up by T cells, a subset of immune cells. A follow-up analysis showed that the virome triggered the immune system to release proteins that prevent too much glucose from being transported into the blood. Without phages, this immune response is blunted and more sugar quickly enters the bloodstream.
The team repeated the experiments using human small intestine organoids – tiny versions of the organ grown from stem cells in the laboratory – populated with human intestinal viruses. They observed a similar relationship between the virome, the immune system and carbohydrate metabolism.
“The fact that the virome can directly stimulate and activate carbohydrate metabolism, a fundamental pathway for energy absorption and conservation, is completely new,” Barr said.
The study also suggests that researchers need to think about viruses when considering gut health, said Corinne Mauricea microbiologist from McGill University who was not involved in the study. “They show that there are interactions between the virome and the immune system that we haven’t appreciated until now,” Maurice told Live Science.
Although the results highlight the importance of viruses in carbohydrate metabolism, researchers are unsure how different types of viruses might affect this process.
Today, Fu wants to develop drugs or other strategies to modify the virome and, therefore, diseases like diabetes. However, experts stressed that much remains to be done to understand how the gut virome behaves in humans, across disease states, before developing potential therapies.
