Many people, when they hear the word “bacteria”, think of dirt or disease. It is true, however, that the trillions of bacteria living in our gut, which make up our gut microbiota, carry out duties that are key to our survival. Not only do they help us digest certain foods and extract nutrients and vitamins, they also educate our immune system and may help protect us from autoimmune diseases, where your immune system attacks healthy cells in your body by mistake. In this sense, a new research performed on mice has found that gut bacteria may play a role in protecting us from inflammatory bowel diseases (IBD), specifically ulcerative colitis.
A team of researchers at the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) in Barcelona and the University of Calgary in Canada has discovered a novel mechanism through which gut microbiota regulates the organism’s immune response, in particular the immune response involved in autoimmune diseases. Their findings have been published in Cell,
“We have observed that a protein expressed by gut microbiota bacteria, called Bacteroides, acts to prevent IBD by recruiting white blood cells to kill an immune system cell that is in charge of orchestrating IBD,” says Kathy McCoy, from the Cumming School of Medicine at the University of Calgary. “We believe this mechanism is probably involved in preventing a lot of people from developing IBD,” she adds.
In the same study, researchers also observed that the protein expressed by the bacteria is almost identical to a protein expressed by insulin-producing cells in the pancreas. The CD8 lymphocytes can mistakenly attack the pancreatic cells and cause type 1 diabetes.
In humans, CD8 lymphocytes react to both the Bacteroides antigen and the pancreatic cells. Researchers sequenced the gut microbiota of 23 individuals divided in 4 groups (healthy, with ulcerative colitis, Crohn’s disease or diabetes) and thanks to genetic sequencing saw that the bacterial protein was present in the four different groups of individuals.
“We still don’t know whether the fact that lymphocytes recognise the gut bacteria’s protein in humans has the same protective consequences against colitis as we see in mice, although we suspect it does” explains in an interview with Gut Microbiota for Health Pere Santamaria, group leader at IDIBAPS and a professor at University of Calgary. He adds: “These lymphocytes exist in the body because they protect individuals against colitis. Nevertheless, the price you have to pay is that, sometimes, these lymphocytes can also react with a very similar antigen expressed in the pancreatic cells, leading to type 1 diabetes.”
“And if we have come across this specific example, it is highly likely there are many other cases of “molecular mimicry” between gut microbial proteins and proteins expressed in specific tissues or organs of the body. These anticipated new cases may help explain relationships between the presence or absence of certain bacteria in the microbiota and changes in the incidence or prevalence of certain autoimmune diseases in the population,” he adds.
As the origin of this cross-reaction is probably related to evolution, now researchers are looking into whether the relationship between the microbiota and the immune system is uni- or bidirectional. In other words, whether the microbiota controls the functioning of the immune system or whether interaction with the organism’s immune system also influences microbiota composition.
Nanjundappa RH, Ronchi F, Wang J et al. A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis. Cell, 2017 DOI: 10.1016/j.cell.2017.09.022
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