P073 DIET AS A MICROBIOME-CENTERED THERAPY FOR IBD

Your food is your best medicine. Nowhere else is this more real than for those suffering from inflammatory bowel disease (IBD). Thus, we developed the IBD-Anti-Inflammatory Diet (IBD-AID™) to relieve IBD symptoms while providing nutrient adequacy. The IBD-AID™ was designed to increase the diversity of bacteria that produce short-chain fatty acids (SCFAs) to modulate the local immune response. After 4 weeks on the IBD-AID™, patients have reported a reduction of symptoms and medication. Our goal is to define diet-microbiome-inflammation interactions that promote health while consuming the IBD-AID™. We posit that IBD-AID™ favors SCFA-producing bacteria resulting in dampening of inflammation and assisting patient’s remission. We recruited 19 patients with mild to severe CD or UC, to determine diet-dependent changes in the microbiota that could support the hypothesis. The study design was a single-arm, prospective, pre-post intervention trial. After a ‘baseline’ period of 4 weeks, the dietary ‘Intervention’ phase started and continued for 8–10 weeks (Fig 1). We performed metagenomic sequencing of 400+ fecal samples and analyzed 300+ food frequency questionnaires. Most (88.2%) patients achieved ≥50% diet compliance. The IBD-AID™ significantly promoted microbiota signatures that have been associated with colonic health. We found that increased intakes of prebiotics foods correlated with the abundance of SCFAs-producing members of the Bacteroides and Parabacteroides. Similarly, increase intakes of probiotics foods during intervention correlated with the abundance of Clostridium bolteae, a bacterium known to play a critical role in the induction of regulatory T cells. We found that vegetable and nuts intake -encouraged in IBD-AID™, correlated with the abundance of butyrate-producing Roseburia hominis, Eubacterium rectale, and Faecalibacterium prausnitzii. The increased abundance of those SCFAs-producing bacteria after the intervention was accompanied by declines in putative pathogenic strains, such as Escherichia sp., Alistipes sp., and Eggerthella sp. The majority (61.3%) of patients treated for at least 8 weeks, who achieved as minimum as 50% dietary compliance reported a dramatic decrease in disease severity. To examine the role of those diet-dependent microbiome signatures in inflammation, we use P-glycoprotein (P-gp) expression as a biomarker. P-gp is an ABC transporter in epithelial cells implicated in the development and persistence of chronic intestinal inflammation in IBD. We found that fecal supernatants from IBD patients adopting the IBD-AID™ induced P-gp expression. Altogether, these results uncover a novel molecular mechanism of the diet-microbiome-immune interaction allowing us to customize dietary guidelines to emphasize foods with known effect on microbiome signatures associated with health. Fig 1. Schematic representation of the study design and sampling schedule.