A new study conducted in the Department of Microbiology and Immunology at the Lewis Katz School of Medicine (LKSOM) revealed that the naturally produced protein curli has anti-inflammatory effects in mice models of inflammatory bowel disease (IBD). The research paper, entitled “Biofilm-associated bacterial amyloids dampen inflammation in the gut: oral treatment with curli fibres reduces the severity of hapten-induced colitis in mice”, was published in Biofilms and Microbiomes, a journal from the Nature Publishing Group.
IBD is a chronic, potentially life-threatening disease caused by an exacerbated and inappropriate immune response, leading to the inflammation of the digestive tract. Most management therapies rely on immunosuppressive medication, which can lead to adverse side effects such as bacterial infection. In order to explore potential new therapeutics for IBD, researchers have been investigating the influence of a protein called curli in the gastrointestinal tract and its potential as an anti-inflammatory agent.
Curli is an amyloid protein secreted by strains of the Enterobacteriaceae family that form the biofilm of bacteria lining the gut. Biofilms are aggregates of bacteria, held together by an extracellular matrix that lines the gastrointestinal tract and contributes to its health and equilibrium. In this context, curli reinforces this epithelial layer, avoiding its disruption, minimizing the risk of inflammation. Curli has been shown to interact with toll-like receptor (TLR) 2, a regulator of anti-inflammatory response in the intestinal mucosa and inducer of expression of the important anti-inflammatory cytokine interleukin (IL)-10.
Researchers observed that in mice with acute colitis, a single dose of curli through oral administration resulted in an up-regulated expression of IL-10 via TLR-2 activation. Moreover, cytokine production was not observed in mice with healthy gastrointestinal mucosa following oral administration of curli, suggesting that its effect is only elicited in the presence of an inflamed gut environment. The treatment effect of the one-time administration of curli was similar to the response of anti-TNF-alpha antibody therapy.
Despite the positive results, researchers suggest that further studies are needed, as factors such as extracellular DNA present in curli fibers can be also eliciting an immune response or activation of other receptors.
Dr. Çagla Tükel, the lead author of the study, commented on the positive results in a press release, “The really remarkable finding is that one dose of curli – not a daily dose, but just a single oral dose – decreased inflammation and disease pathology and altered the cytokine profile.”
Biofilm products in general and curli fibers in particular prove once again to be an interesting and promising research area in the pursuit of new therapies for IBD.