A recent discovery could help to explain further why living with dirt can benefit human health. Scientists have found that a bacterium that lives in soil makes an anti-inflammatory fatty acid that can promote resilience to stress. 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 fatty acid has the name 10(Z)-hexadecenoic acid, and the team used "next-generation sequencing techniques" to investigate its interaction with macrophages, a type of immune cell. 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. Soil bacterium has a direct, protective effect "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. 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. Another side of the hygiene effect Decades ago, before more sophisticated analysis techniques were available, scientists could see little of what happened at molecular levels in cells. All they could show was that exposure to microorganisms appeared to benefit health. Those studies led British scientist David Strachan to coin the term "hygiene hypothesis" in 1989. The theory states that the more people's modern lives distance them from the land and contact with farm animals, so their bodies miss out on the collaboration with microorganisms. This damages the immune system and increases the risk of allergy and asthma. At first, the assumption behind the hygiene hypothesis was that exposure to potentially harmful microorganisms helped the immune system to develop resilience against them. 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 microbes 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 behavior as antidepressants. The treatment also appears to have a lasting anti-inflammatory effect on the brain. Research has suggested that too high an inflammation response can raise the risk of post-traumatic stress disorder (PTSD) and other stress-related conditions. Could a 'stress vaccine' be in sight? Lowry and his team also did another study in which they showed that treating mice with M. vaccae could prevent them from developing a reaction that is similar to PTSD after experiencing a traumatic event. Mice that they treated with the bacterium were also less likely to develop stress-related colitis and display anxiety under future stressful circumstances. The team sees possibilities in developing M. vaccae as a "stress vaccine." This could help to protect people with high-stress occupations — such as soldiers and firefighters — from developing stress-related psychiatric illnesses. There could also be scope for developing a drug that targets the fatty acid. Further studies would first need to confirm that the fatty acid does indeed have therapeutic potential. Lowry says that their study is just exploring "the tip of the iceberg in terms of identifying the mechanisms through which [soil bacteria] have evolved to keep us healthy." "This is just one strain of one species of one type of bacterium that is found in the soil, but there are millions of other strains in soils." - Christopher Lowry Source
