Dextran Sodium Sulfate (DSS) Induces Colitis in Mice by Forming Nano-Lipocomplexes with Medium-Chain-Length Fatty Acids in the Colon

Abstract

Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ∼200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity.

Control of inflammation by stromal Hedgehog pathway activation restrains colitis

“…To investigate the role of Hh signaling in IBD, we first tested whether Gli1 inactivation increases the severity of acute dextran sulfate sodium (DSS)-induced colitis in mice (7). We obtained inconclusive results, quite distinct from those previously reported (Fig.…”

High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer

“…Contrary to this and consistent with our findings, Boddicker et al showed that a high-fat lard-based diet (60% kcal from fat) significantly decreased total colonic lesions compared with a LFD in male C57BL/6 mice (5). Of further interest is the study of Laroui et al, whose findings suggest that DSS is responsible for colitis development by forming "nanolipocomplexes" with MCFAs in the colon (27). Other studies have also shown that DSS treatment paired with HFD consumption produces a more aggressive form of colitis than DSS coupled with a LFD (17,29,40,41).…”

Murine Models of Inflammatory Bowel Disease (IBD)

“…DSS colitis has been attempted using many different mouse strains with varying degrees of success. The current hypothesis of how colitis-inducing injury occurs is that DSS is directly toxic to the gut epithelium (Laroui et al 2012). The loss of epithelial integrity and subsequent migration of bacteria into the crypt results in inflammation and triggers a pathologic loss of structure.…”

“…In contrast, disease activity scores such as diarrhea and presence of occult blood are typically not quantitative enough to be meaningfully correlated with pathology (i.e., these are binary readouts) and are not used in balancing cohorts. When available, more sophisticated techniques such as endoscopy can be employed to assess colon damage and group animals (Laroui et al 2012). In contrast to colitis models, ileitis models do not positively correlate with body weight loss, and visualization of the mouse ileum is not possible using endoscopy methods.…”