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Tough to overcome obesity? The gut microbiome might to blame

The gut microbiome is widely viewed as potential target for novel therapeutics, and not just for its role in gastrointestinal conditions such as inflammatory bowel disease. Now scientists are providing fresh insights into how intestinal bacteria contribute to obesity.

Microbiologist Christoph Thaiss and his team at the University of Pennsylvania discovered that changes to the biological clock, coupled with a previous history of obesity, can disrupt the activity of the gut microbiome and increase susceptibility to obesity.

The findings, which were published in the journal Science, helped Thaiss win the 2018 Science & SciLifeLab Prize for Young Scientists.

For their study, Thaiss and his colleagues uncovered microorganisms in the digestive tracts of both mice and people that have a biological clock that ticks in a daily pattern. Any disruption of the regular cycle—either by genetic modification or an environmental factor like jet lag—can also change the microbiome’s rhythm. That triggers a cascade effect that makes mice and humans more prone to becoming obese, according to a press release.

Obese individuals who successfully lose weight often fail to keep the pounds off—a phenomenon known as the “yo-yo effect.” Thaiss’ team found that a period of obesity changes the composition of mouse microbiomes for a long period of time, raising the risk of fast weight rebound.

That finding seemed to confirm a 2016 Nature study by Israeli scientists that suggested that the intestinal microbiome somehow retains an obesity “signature” that persists after successful dieting and contributes to faster weight relapse, even on a normal diet. Researchers in that study suggested that modulating flavonoids could hold potential as novel therapeutics for weight management.

Previous research has linked the gut microbiome to metabolic disorders like obesity and diabetes. A Nature study in 2006 observed a higher ratio of Firmicutes to Bacteroidetes bacteria in obese mice. Other scientists have been looking for ways to use the body’s own resources to fight obesity. For example, a team at Georgetown University recently found the naturally occurring protein FGFBP3 can help mice fight obesity.

As part of his research, Thaiss examined why individuals with metabolic disorders are more susceptible to inflammation. His team found that obese and diabetic mice suffer damage to their intestinal epithelial cells. That allows bacterial products to pass into the bloodstream and cause inflammation, the researchers believe.

The various microorganisms that inhabit the human gut continue to inspire new ideas for tackling a variety of diseases. In a deal potentially worth $534 million, Genentech recently tapped Microbiotica to leverage gut bacteria for research into inflammatory bowel disease. Kaleido Biosciences, which just collected $101 million in a series C funding round, is looking to direct the microbiome’s metabolic output for treating several disorders. And Axial Biotherapeutics is targeting the gut microbiome for treating central nervous system disorders.

Thaiss hopes to validate his team’s theories further in human studies. “Our first insights indicate that the fundamental mechanisms we discovered can be applied to human biology,” he said in the release. “Whether our approach can be used to improve metabolic health in humans is an exciting question that we are actively pursuing.”