Microbes residing throughout the human body are now being appreciated for their contributions both to human health and disease. Scientists have shown that the community of microbes living in the human gut have “co-evolved” with their host to the point that a well-balanced gut microbial community is essential for healthy functioning of the digestive system, as well as the immune system, to prevent conditions such as inflammatory bowel diseases (IBD) and other inflammatory or autoimmune conditions. For example, gut microbes perform many functions that humans are incapable of, such as harvesting certain nutrients from the foods we consume. Some bacterial species break down dietary fiber into short-chain fatty acids in the large bowel. These fatty acids have been shown to have a beneficial, anti-inflammatory effect on conditions such as IBD, and are known to act directly on cells in the gut or elsewhere by latching onto components of the cell’s surface known as “receptors,” including one called GPR43 in humans, or Gpr43 in mice.
In this study, researchers aimed to identify the mechanism by which this type of fatty acids, produced as a result of bacterial fermentation of dietary fiber, have a protective effect against IBD and other inflammatory conditions, such as arthritis and asthma. They showed that the presence of intestinal bacteria reduces disease severity using a mouse model that mimics a form of IBD known as ulcerative colitis. For this experiment, they compared mice raised conventionally with those raised in a bacteria-free environment, before and after their guts were repopulated with bacteria. Based on prior knowledge of microbial effects on IBD via production of short-chain fatty acids, which act through receptors like GPR43, the scientists utilized microarray screening technology to identify immune cells that produce high amounts of GPR43/Gpr43 in humans and mice, respectively. In mice genetically engineered to lack Gpr43 and treated to model ulcerative colitis, immune cells did not respond normally to short-chain fatty acids, and these fatty acids did not reduce intestinal inflammation as in wild-type mice. The results of this experiment indicate that short-chain fatty acids act through Gpr43 on the surface of immune cells to exert their protective effect against intestinal inflammation. Similar results were seen in mouse models of arthritis and allergic airway inflammation.
This study identifies how interactions between by-products of bacterial metabolism and a receptor on the surface of immune cells act to protect against IBD and other inflammatory conditions, such as rheumatoid arthritis and allergic inflammation of the airways. These interactions could provide a target for manipulating immune responses in these conditions through such means as diet and prebiotic/probiotic supplementation.
Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461: 1282-1286, 2009.