A217 DEFINING THE RELATIONSHIP BETWEEN DIETARY FIBERS AND INFLAMMATORY RESPONSE IN PEDIATRIC INFLAMMATORY BOWEL DISEASES

Abstract

Abstract Background The incidence rates of inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC) are increasing in children. Although the etiology of IBD is poorly understood, factors such as urban lifestyle, diet, increased hygiene, and reduced microbial biodiversity have been implicated as risk factors. Compositional changes and reduced microbial biodiversity have been linked to therapy failure in pediatric IBD. Non-digestible dietary carbohydrates, such as fiber, must undergo fermentation by gut microbiota within the large bowel, producing short chain fatty acids (SCFAs). Animal studies have shown that dietary fibers can inhibit IBD-associated inflammation, and clinical trials have demonstrated that SCFAs can prevent intestinal atrophy and allow for tissue recovery in IBD patients. In disease settings with altered gut microbes, fermentation of dietary fibers may be greatly affected. Unfermented fibers interact with receptors on host immune cells and can induce proinflammatory immune response, production of oxygen species and inflammation, or an inhibition of proinflammatory receptors. Aims Based on this rationale, we hypothesize that dysbiosis in the IBD gut leads to decreased fiber fermenting microbes, resulting in reduced SCFA production. This contributes to increased inflammatory responses both in in vitro cell lines, as well as ex vivo patient biopsies. Because intact fibers can bind to host cell receptors, this promotes inflammatory response and continued dysbiosis. Methods To assess effects of intact fiber on immune cells, macrophage and T-cell in vitro cultures were used to measure cytokine response to inulin (5mg/mL) and oligofructose (5mg/mL) through ELISAs/qPCR. These cell lines and ex vivo patient biopsies were treated with whole fibers and IL-1β secretion was measured. Fibers were also pre-fermented with microbes of interest or whole microbe patient intestinal washes and used to treat cell lines and patient biopsies. Results Whole fibers induced a pro-inflammatory response in macrophage cells but not T-cells, and this pro-inflammatory response was mitigated by pre-fermenting the fibers. Intestinal washes from severe IBD patients were unable to successfully ferment oligofructose or reduce fiber-associated inflammation in macrophage cell lines, whereas washes from remission or non-IBD samples reduced IL-1β. Oligofructose was found to increase IL-1β secretion in UC and CD patient biopsies, but not in non-IBD specimens. This increase was also correlated with disease severity. Conclusions These results indicate that a lack of fiber-fermenting microbes and presence of whole fibers can lead to pro-inflammatory responses, both in cell lines and patient biopsies. However, the presence of appropriate fermenting microbes can reduce fiber-associated inflammation. Funding Agencies CCCWCHRI, Weston Foundation