Targeting gut inflammation through diet: a tailored American diet for patients with ulcerative colitis

University Of Miami School Of Medicine, Coral Gables FL

Investigators

Abstract

Ulcerative colitis (UC) is a chronic and devastating immune-mediated disease. Despite growing evidence of the importance of diet in UC, few clinical trials have examined the impact of diet on inflammation–especially among Americans. The long-term goal of our team is to develop evidence-based, personalized dietary treatments for UC that consider individual patient factors, including tailored food preferences, to improve both disease inflammation and adherence. From our pilot data, we have evidence that a prudent low-fat/higher diet—even with American food staples—may help to decrease disease inflammation compared to Western diets and that stool microbiome signatures may guide future flares. We also have pilot data from my K23 cohort suggesting that patients with UC carry polyunsaturated fatty acids (PUFA) pathway genetic variants in enzymes that alter the imbalance of n-6 to n-3 PUFA ratios in the blood and tissues. These levels in prior studies have been associated with UC risk. The overall objectives of this study are then to test the effect of an American-tailored low-fat (<3:1 ratio of n-6 to n-3), high fiber diet on disease remission in American patients with mild to moderate UC. We will also test whether baseline individual factors, such as the stool microbiome composition and circulating blood levels of PUFAs, impact diet-mediated inflammation. The central hypothesis is that patients will have a greater likelihood of achieving disease remission by week 8 on the American-tailored low-fat/high-fiber diet than when on their usual diet. Further, individual factors such as stool microbiome composition and PUFA blood levels will predict response to diet therapy. The central hypothesis will be tested by pursuing three specific aims: 1) Determine the effect of an American-tailored anti-inflammatory diet on UC inflammation; 2) Identify the microbiota composition and functional metabolites that mediate the relationship between diet and UC inflammation; and 3) To define the role of PUFA metabolism in modulating intestinal inflammation in UC. Under the first aim, we will evaluate the efficacy of an American-tailored, high fiber and low-fat diet using a cross-over design on 122 patients with mild to moderate UC. Our primary outcome will be clinical and biochemical remission using the validated simple clinical colitis index (SCCAI) and Fecal Calprotectin (FC) at week 8. Patients will receive catered meals for the diet intervention and stipends for groceries when on the placebo diet. Under the second aim, we will examine microbiota abundance and microbiota-derived metabolites at baseline and those associated with changes occurring from the diet intervention and among responders/non-responders to the diet. The third aim examines the influence of PUFA metabolism (including PUFA serum levels) as predictors of disease inflammation and response to diet. The proposed research is significant because we are developing an evidence-based anti-inflammatory diet for UC tested in a controlled clinical trial that also considers local, affordable foods for Americans, which is unprecedented in prior studies. Our research is innovative because it is the first attempt to tailor dietary therapy in UC that examines individualized predictors of response to diet.