Removing single gene from gut bacteria found to alter host's metabolism
The bacteria that call your gut home can have a tremendous impact on your overall health, but exactly how the bugs do so is a web that's still being untangled. To investigate, researchers at Harvard Medical School have deleted a single gene from one gut bacteria species and found that it alters the metabolism of the host, reducing their weight gain.
In recent years, scientists have implicated a person's gut microbiome in their likelihood of developing diabetes, obesity, multiple sclerosis, Alzheimer's and even depression, but it's tough to figure out which bacteria are responsible for which effects, and how they trigger them.
For the new study, the researchers focused on a single aspect of the gut environment, and investigated how bacteria can change that to affect the host's metabolism. The aspect in question is a group of substances called bile acids, and imbalances in these are thought to contribute to obesity. Gut bacteria can either help or hinder that balance by chowing down on these acids, using enzymes known as bile salt hydrolases.
"Previous research has shown that these hydrolases play an important role in regulating host metabolism, but not exactly how," says Sloan Devlin, senior author of the study. "We took a novel approach to understanding the role of these enzymes by controlling the activity of a selective bile salt hydrolase in the mouse gut."
To do so, the team experimented with the species Bacteroides thetaiotaomicron, which metabolizes certain bile salts. By removing a single gene, they engineered one group of the bacteria so that it couldn't metabolize those bile salts, then introduced the colony into mice that had no other bacteria strains in their gut. They did the same with the natural B. thetaiotaomicron, and compared the effects of the two groups on the metabolism of the host mice.
As expected, the mice containing the engineered bacteria had much higher levels of those bile salts, since they weren't being metabolized. The researchers then turned their attention to what effects those extra bile salts had on the mice themselves. Interestingly, those colonized with the engineered bacteria gained less weight than the control mice, they had lower levels of fat and cholesterol in their blood and liver, and would metabolize fats more readily for energy.
"Previous work has shown that the microbiome as a whole affects metabolism, but our paper provides a more reductive view," says Devlin. "By showing that deleting a single gene results in downstream changes in the host metabolism, we establish this particular gene as a potential target for future drug development and provide a step towards a fuller understanding of how the microbiome affects metabolism."
Metabolism wasn't the only thing affected either. After conducting genetic analysis, the team discovered changes in genes related to the circadian rhythm and immune response, suggesting bile acid has a much wider range of effects in the body.
The research was published in the journal eLife.
Source: eLife Sciences