Most people have never heard about a protein called vinculin, but a recent study of 165 IBS, 30 IBD and 26 healthy controls found that people with IBS have higher levels of (auto) antibodies to this protein than do healthy controls or people with inflammatory bowel disease. One possible outcome of this work is a specific diagnostic blood test for IBS that can distinguish this condition from IBD. But the findings from this multicenter study, led by Dr. Mark Pimentel of Cedars-Sinai Medical Center in collaboration with researchers from Beth Israel Deaconess Medical GAS in Boston could shed more light on how IBS develops and lead to alternative treatment approaches for this condition.
Vinculin is what’s called a “cytoskeletal protein”, and is found at junctions between cells as well as junctions between cells and extra cellular matrices. Vinculin appears to help anchor a filamentous protein called F-actin which helps muscles contract, but also helps the immune system fight off pathogenic bacteria.
One cause of IBS is having a previous bout of gastroenteritis (a gut infection) which often triggers small intestinal bacterial overgrowth (SIBO). The idea behind this study is that a bacterial toxin called cytolethal distending toxin B (CdtB) produced by gram negative Proteobacteria (such as Shigella sp. and E. coli), triggers gastroenteritis by molecular mimicry which stimulates auto-antibodies to vinculin. This process may be involved eventual development of IBS, though the details of how this happens are far from clear. Studying antibody titers to vinculin in IBS patients can establish the role of gastroenteritis in IBS and help determine the extent to which autoimmune processes are involved.
Clearly vinculin is relevant to gut infections as another study showed that Shigella flexneri(another Proteobacteria pathogen), which causes a form of dysentery, secretes an invasion protein called IpaA which binds to the vinculin to facilitate the bacteria’s entry into cells that line the intestine. How this all ties together will be an interesting story to follow.