P0595Impact of the novel UC-TREAT diet on the gut microbiome and its tolerability in healthy adults and adults with quiescent ulcerative colitis

Background Microbiome modifying treatments show potential in favourably influencing outcomes of patients with mild-moderate Ulcerative Colitis (UC). In a proof-of-concept study, we tested the gastrointestinal tolerability of a novel, “eubiotic” diet (UC-TREAT), and assessed its effects on the gut microbiome and short chain fatty acid (SCFA) production in individuals with UC and healthy controls (HC). Methods In a controlled prospective trial, 36 adults (18 HC and 18 with quiescent UC, defined as SCCAI ≤5) underwent a 10-day “run-in” phase, followed by a 5-day introductory “ramping” phase, and a 10-day “full” dietary intervention with UC-TREAT. UC-TREAT is rich in fermentable carbohydrates (providing 35g/day fibre in addition to habitual intake), and includes daily consumption of 5 different fermented foods, 2 types of berries, and a multivitamin supplement. Faecal samples were collected before and after each study phase, in which microbiome (16S rRNA), bacterial load (quantitative PCR), SCFA (GC-FID) and faecal calprotectin (FCAL) were assessed. Gastrointestinal tolerance (GSRS-IBS), disease activity (SCCAI) and dietary intake were assessed throughout the study. Results Fibre intake doubled during UC-TREAT (9.8 vs 20.8g/1000kcal/day, p < 0.001) and fermented food consumption increased by 4.3 portions/d (p < 0.001) in all participants. In both participant groups, an increase was observed in faecal acetate [median (Q1:Q3) µmol/g: UC: +11.1 (-3.73, 21.5); HC: +15.2 (-0.57, 36.6), both p < 0.01], total SCFA [UC: +11.6 (2.38, 22.1) µmol/g, p = 0.006; HC: +23.1 (-0.76, 53.2), p = 0.015], and bacterial load [log10 16S rRNA gene copies/g, UC: +0.07 (0, 0.22), p = 0.03; HC: +0.06 (-0.04, 0.14), p = 0.07]. Butyrate also increased in UC participants [+2.79 (-0.75, 4.88) µmol/g, p = 0.03). UC participants reported a short-term increase in bloating [median score: +2 (0, 4.3), p = 0.012], while HC reported prolonged bloating [+2.5 (1, 3), p = 0.001] and a transient rise in constipation [+1 (0, 3), p = 0.03] and satiety [0 (0, 1), p = 0.03]. Disease activity score increased [0 (0, 1), p = 0.012], while all UC participants remained in clinical remission and FCAL remained unchanged in UC, but decreased in HC [-3.15 (-10.3, 0.71) mg/kg, p = 0.02]. Microbiome composition changed in UC patients (R2=1.2% p < 0.01), but not in HC; Abundance of Streptococcus, and Anaerostipes hadrus, a butyrate producer, increased in UC (p < 0.001). Conclusion UC-TREAT increased fibre-originating faecal SCFA, bacterial load, and SCFA-producing taxa, without negatively affecting FCAL or GI tolerance in quiescent UC. These proof-of-concept results should be replicated in a larger, well-controlled RCT. Conflict of interest: Ms. Mckirdy, Shona: No conflict of interest Gaya, Daniel: No conflict of interest Russell, Richard K.: Grant: Nestec Other: Abbvie, Celltrion, Janssen, Lilly, Nestle, Pharmacosmos, Pfizer Hansen, Richard: Personal Fees: Dr Hansen has received consultancy fees and travel support from 4D pharma. Macdonald, Jonathan: No conflict of interest Seenan, John Paul: No conflict of interest Nichols, Ben: No conflict of interest Koutsos, Athanasios: No conflict of interest Gerasimidis, Konstantinos: Grant: Nestle Health Science, Nutricia-Danone, Mylan Personal Fees: Abbott, Baxter, Nestle Health Science, Nutricia-Danone, Servier, Janssen