Viruses gleaned from healthy feces fight obesity in mice

Altering the gut microbiome by transplanting the stool contents from a healthy donor is emerging as a promising way to treat a variety of conditions, including everything from autism to inflammatory bowel disease to cancer. Scientists looking to this technique as a way of treating obesity have found some early success in mice, after implanting virus particles gleaned from the feces of lean mice curtailed weight gain and progression of a precursor of type 2 diabetes.

The work was carried out by scientists at the University of Copenhagen and focuses on a relatively new arm of fecal transplant science, where some contents of the stool are first separated from the others. Unlike typical fecal transplants where the stool in its entirety is administered to the patient, this technique first filters out the live bacteria from the sample, while upping the concentration of virus particles known as bacteriophages at the same time.

These viruses can alter the gut microbiome on their own by specifically targeting and attacking bacteria, and are themselves an area of intense focus for some scientists in the field. Previous research has shown how these predators can trigger a cascade of effects on the microbial communities in our bellies, while the technique could also avoid some of the risks of disease transmission that come with transplanting live bacteria.

In exploring the potential of this approach to tackle obesity and diabetes, the University of Copenhagen team hoped to correct imbalances in the gastrointestinal microbiome that are thought to underly these conditions. In doing so, the team looked to build on recent research indicating that the makeup of viruses in the gut play an important role in keeping things stable.

“If one eats poorly for long enough, they risk creating an imbalance in their intestinal tract,” says senior author Dennis Sandris Nielsen. “Here, we have a means of recuperating balance by shooting missing virus particles back into the system.”

To begin with, the scientists fed one group of mice a standard low-fat diet for a period of time, and then collected their feces and filtered out all the live bacteria. The resulting virus particles were then transplanted into mice that had been feeding on a high-fat diet for six weeks. These mice continued with these eating habits for a further six weeks, and were then assessed for weight gain and glucose tolerance.

When they were compared to a control group on a high-fat diet but without the transplanted viruses, the mice that received the virus particles exhibited significantly decreased weight gain. The technique also showed promise against glucose intolerance, a common indicator of type 2 diabetes, with the team observing no difference in how the treated mice responded to a shot of glucose compared to the healthy control group.

“In the obese mice on high fat diet, that didn’t receive the virus transplant, we observed decreased glucose tolerance, which is a precursor of diabetes,” explains Torben Sølbeck Rasmussen, first author of the study. “Thus, we have influenced the gut microbiome in such a way that the mice with unhealthy lifestyles do not develop some of the common diseases triggered by poor diet.”

There are a few caveats when applying the results of this research to conditions of obesity and type 2 diabetes. While the team says the study suggests the technique could have a similar effect in humans, years of trials would be needed to establish its safety and efficacy. And even then, it would be unlikely to constitute a standalone treatment for general obesity – rather, it would need to be used alongside dietary changes to treat more serious cases of the condition.

The research was published in the journal Gut.

Source: University of Copenhagen

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