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Researchers at the University of Colorado Boulder (CU Boulder) led a study that investigated Mycobacterium vaccae, an environmental bacterium that feeds on decaying organic matter. Previous studies with cells and laboratory animals have shown that M. vaccae can reduce inflammation and protect against stress.
However, as the authors explain in a recent Psychopharmacology paper about their work, “the molecular mechanisms underlying anti-inflammatory effects of M. vaccae are not known.” In the new study, the researchers “purified and identified a unique anti-inflammatory triglyceride” from the soil bacterium. They then synthesized and tested the “free fatty acid” version of the fat in mouse immune cells.
The researchers saw that the fatty acid bound to a particular receptor, or signaling protein, in the cells. This event, in turn, blocked a number of inflammation-driving molecular pathways. The name of the receptor is peroxisome ‘proliferator-activated receptor (PPAR)’.
Further experiments revealed that treating the immune cells with the fatty acid before stimulating them increased their resistance to inflammation.
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“We think,” says senior study author Christopher Lowry, an associate professor of integrative physiology at CU Boulder, “[that] there is a special sauce driving the protective effects in this bacterium, and this fat is one of the main ingredients in that special sauce”. He says that the finding is “a huge step forward for us because it identifies an active component of the bacteri[um] and the receptor for this active component in the host.”
The interaction between the anti-inflammatory fatty acid and immune cells is a product of the coevolution of humans and soil bacteria, Lowry argues. Macrophages are immune cells that eliminate pathogens, such as bacteria, by consuming them. They play a central role in inflammation.
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It seems, says Lowry, that once the soil bacterium gets inside the immune cell, it releases the anti-inflammatory fatty acid. This then binds to the PPAR and closes down the “inflammatory cascade”. The findings are further evidence that contact with soil bacteria helps human health in ways that are different from what scientists once thought.
However, researchers such as Lowry and his team are redefining the hygiene hypothesis to add another side of the coevolution story. It is not just that exposure to disease-causing bacteria can prime immunity, but also that beneficial soil microbe can actively boost health through direct molecular interaction with immune cells. In previous work, Lowry has demonstrated several ways in which exposure to beneficial bacteria appears to be good for mental health.
One study, for instance, showed that children that grow up on farms with animals have immune systems that are more resilient to stress, and they are also less likely to develop mental illnesses than children that grow up in the city without pets. Another study showed that injecting rodents with M. vaccae has a similar effect on behaviour as antidepressants. The treatment also appears to have a lasting anti-inflammatory effect on the brain.