U.S. Department of Health and Human Services

Particles Released from a Gut Microbe Protect Against Colitis

​​A team of scientists has discovered how a species of gut bacteria interacts with the immune system to suppress inlammatory bowel disease (IBD), in a study in mice. IBD is the general name for the diseases, such as Crohn’s disease and ulcerative colitis, that cause symptoms such as abdominal pain and diarrhea due to inlammation and irritation in the intestines. Bacteroides fragilis (B. fragilis), a species of bacteria that inhabits the human intestinal tract, can suppress inlammation in diseases like IBD. This type of bacteria makes a molecule called polysaccharide A, which not only protects the bacteria from the harsh environment of the intestine, but also activates a group of immune cells called regulatory T cells that inhibit inlammation by restraining the immune response. However, exactly how B. fragilis interacts with the immune system through this bacterial molecule was a mystery.

A group of researchers tackling this question found that polysaccharide A is released from cultures of B. fragilis in small spheres, called outer membrane vesicles (OMVs), which bud from the bacterial cells’ outer coating. When given to mice orally, these OMVs prevented an experimental form of colitis. When OMVs were added to immune cells in laboratory culture, polysaccharide A was found to accumulate in a type of immune cell called a dendritic cell, which communicates with regulatory T cells to activate them. This is particularly important in the gut, because dendritic cells have the key role of sampling intestinal contents to coordinate T cell reactions. When OMVs were added to cultures containing both dendritic cells and T cells, there was an increase in the production of an anti-inlammatory chemical produced by the T cells. The researchers predicted that a dendritic cell protein called TLR2, which senses bacterial products, was necessary for this response. Indeed, when OMVs were added to dendritic cells that were lacking TLR2, the dendritic cells did not cause an increase in the anti-inlammatory chemical in T cells. In support of this, the scientists found several TLR2-dependent genes that were turned on in dendritic cells by polysaccharide A, including a gene called Gadd45a, which is required to promote T-cell response. Mice that were genetically manipulated to lack the Gadd45a gene were not protected against colitis when they were treated with OMVs, unlike the non-genetically manipulated mice. This study demonstrates a fascinating interaction on a molecular level between a gut microbe and the immune system of its mouse “host” that leads to protection against disease. More importantly, it opens the possibility for future research in humans that could potentially lead to new therapies for inlammatory bowel disease.

Shen Y, Giardino Torchia ML, Lawson GW, Karp CL, Ashwell
JD, and Mazmanian SK. Outer membrane vesicles of a
human commensal mediate immune regulation and disease
protection. Cell Host Microbe 12: 509-520, 2012.