DIETARY FIBER GUAR GUM EXACERBATES COLONIC INFLAMMATION IN MULTIPLE EXPERIMENTAL MODELS OF INFLAMMATORY BOWEL DISEASE

Abstract The role of fermentable dietary fibers in patients with inflammatory bowel disease (IBD) is not understood. Herein, we elucidated the effect of dietary fiber guar gum, commonly added to a wide range of processed foods, on colonic inflammation. The use of three different IBD models allowed us to examine the effect of guar gum on various aspects of human IBD, such as immune hyperactivity [IL-10 receptor (IL-10R) neutralization], epithelial injury [dextran sulfate sodium (DSS)], and infection [Citrobacter rodentium (CR)]-mediated inflammation. Wild-type (WT, C57BL/6) mice fed either control cellulose (insoluble fiber, aka non-fermentable fiber) or guar gum (soluble fiber, aka fermentable fiber, 7.5% w/w) were administered four weekly injections of IL-10R neutralizing antibody (α-IL-10R) to induce immune-hyperactivation mediated chronic colitis. Guar gum treated mice developed robust α-IL-10R mediated colitis. Guar gum fed mice had splenomegaly, colomegaly, elevated systemic proinflammatory markers [serum amyloid A (SAA), lipocalin 2 (Lcn2) and keratinocyte-derived chemokine (KC)] and elevated colonic Lcn2 and interleukin (IL)-1β, and histopathology scores compared to control, cellulose-fed, mice. Similar results were observed in Toll-like receptor 5 deficient mice, which are prone to develop microbiota-dependent colitis. Next, to examine the effect of guar gum on the epithelial injury model, mice were treated with DSS (1.4% w/v in drinking water) for seven days. The guar gum fed group developed severe colitis, including reduced body weight, diarrhea, rectal bleeding, shortening of colon length, and elevated levels of pro-inflammatory markers (Lcn2, KC, and SAA)compared to the control group. The last model to be tested was infection-induced colitis. Since inflammation is required to clear the infection, we hypothesized that guar gum fed mice might clear CR infection better than controls. To our surprise, guar gum fed WT mice shed higher numbers of CR in the feces than the cellulose group. The guar gum fed mice had lower body weights, colomegaly, an elevated level of colonic and serum Lcn2, and higher serum SAA than the control group. Collectively, guar gum failed to protect against CR-induced colonic pathology. Altogether, the work demonstrates that guar gum feeding may exacerbate colonic inflammation following immune-hyperactivation, chemical, and infectious injury. Cautioning IBD patients to monitor their consumption of guar gum fiber might be a way to reduce the severity of intestinal inflammation.