Single treatment with curli fibres ameliorates TNBS colitis. Colitis was induced in 6–8-week female Balb/c (n=6–7) mice by intrarectal instillation of 1% TNBS in 50% ethanol or 50% ethanol as a vehicle control. Day 1 post TNBS enema, mice were administered treatments as follows: 0.1 mg curli (oral), 0.4 mg curli (oral), 0.1 mg anti-TNFα (i.p.) or no treatment. (a) survival (n=6), (b) histopathological scores at day 6 post TNBS induction were plotted and (c) H&E images were taken. (d) Stool consistency scores were determined at day 3 post TNBS induction. It should be noted that larger areas of immune cell infiltration and lymphoid follicles in the submucosa was determined in the colonic tissue of mice treated with TNBS alone as compared with the groups that received curli treatment (*P<0.05; **P<0.01; ****P<0.0001). H&E, hematoxylin and eosin; i.p., intraperitoneal; TNBS, 2,4,6-trinitrobenzene sulphonic acid; TNF, tumour necrosis factor; Tx, treatment. Credit; http://www.nature.com/articles/npjbiofilms201519/figures/4
The possibility of taking one pill to bring long-lasting relief might seem too good to be true for inflammatory bowel disease (IBD). Scientists are on the brink of making that happen, thanks to a recent proof-of-concept study, in which the severity of a form of IBD in mice was dramatically reduced with one oral dose of a protein curli isolated from a bacterial biofilm.
Curli is one of the first biofilm-based products to be investigated specifically for the treatment of inflammatory bowel disease, or IBD – a condition that affects as many as 1.3 million people in the United States but for which few safe treatment options exist. Most IBD therapies suppress the immune system, which reduces inflammation but also increases the risk of severe side effects, including cancer and infection.
According to Dr. Tükel, as biofilms and their products are naturally occurring, they are of emerging interest in the realm of gastrointestinal therapeutics. The aggregates of bacteria that make up biofilms are held together by an extracellular matrix, which enables the organisms to form thick protective films over surfaces. Protective biofilms typically produce and secrete substances that are beneficial to the health of the host. Curli, for example, acts to reinforce the epithelial barrier in the intestinal tract — the disruption of which is the central feature of intestinal inflammation.
In vitro, the protein activates toll-like receptor 2, which triggers the production of an anti-inflammatory cytokine known as interleukin-10 (IL-10). Following a single oral dose of curli, mice with acute colitis had increased IL-10 levels and a significant reduction in intestinal inflammation. The main readouts on pathology and weight gain in mice treated with curli were comparable to those observed with standard antibody therapy for IBD.
“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,” Dr. Tükel said.
The findings open the way for further investigation of curli as a novel immunotherapy for IBD or even development as an oral supplement. Additional study of the mechanism by which curli operates also could lead to the identification of new pathways underlying IBD and intestinal inflammation. http://www.eurekalert.org/pub_releases/2015-10/tuhs-slb102815.php
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