A gut bacterium's guide to building a microbiome: Unlike invading pathogens, which are attacked by the immune system, certain good bacteria in the gut invite an immune response in order to establish robust gut colonization -- ScienceDaily
The particular species is found abundantly in the large intestines of many mammals, including humans, and was previously shown by the Mazmanian lab to protect mice from certain inflammatory and neurological disorders such as inflammatory bowel disease and multiple sclerosis. Interestingly, though there are multiple strains of B. fragilis, healthy people form a long-term, monogamous relationship with only a single strain.
"Studies by other labs have shown that most people carry the same strain of B. fragilis throughout their lives," says Donaldson. "We wanted to understand at a molecular level how these bacteria are able to colonize the gut in a stable, long-term way."
First, the researchers aimed to examine B. fragilis's symbiotic relationship with the gut by physically looking at the locations where the bacteria reside. Using electron microscopy imaging on samples of mouse intestines, the team was able to see that B. fragilis clumps together in aggregates deep within the thick layer of mucus lining the gut, nestled close to the epithelial cells that line the surface of the intestine. Donaldson and his collaborators theorized that this spatial niche is necessary for a single species to settle in and establish a stable foothold.
The team next aimed to determine what mechanisms allow B. fragilis to colonize such a niche within the gut. They found that each B. fragilis bacterium is encased in a thick capsule made of carbohydrates. The capsule is typically associated with pathogens (bad bacteria) attempting to cloak themselves from recognition by and attack from the body's immune system. Mutant bacteria lacking this capsule cannot aggregate and do not inhabit the mucosal layer. Thus, the researchers theorized that capsular carbohydrates are necessary for B. fragilis strains to monopolize their niche in the gut.
Because bacterial capsules were known to be related to an immune response in pathogenic bacteria, Donaldson and Mazmanian hypothesized that there may also be an immune response to the B. fragilis capsule. Indeed, they found that antibodies, immune proteins that grab onto and mark specific bacteria or viruses for other immune cells to engulf and destroy, were binding to the B. fragilis capsule in the intestine. One particular kind of antibody, immunoglobulin A or IgA, is found throughout the gut -- in fact, it is the most abundantly produced type of antibody in humans -- but its specific functions have been enigmatic.