P007 Paradoxical effects of high and low emulsifier diets on intestinal permeability in unstressed and stressed states in healthy human adults: a pilot randomised controlled feeding trial.
Fitzpatrick, J.(1)*;Gibson, P.R.(1);Taylor, K.M.(2);Halmos, E.P.(1);
(1)Monash University, Department of Gastroenterology, Melbourne, Australia;(2)Alfred Health, Department of Gastroenterology, Melbourne, Australia;
Background
In preclinical models, high doses of specific emulsifiers induce intestinal inflammation. How these findings translate to Crohn’s disease (CD) is unclear, but the effects of dietary emulsifiers in the context of our food supply are needed before safe evaluation in a CD population. Aims: To develop novel trial healthy diets matched for all dietary components, except emulsifiers; and to evaluate their suitability for study in patients with CD by defining, in healthy subjects, tolerance, blinding and adherence to the diets and their impact on intestinal permeability with and without stress.
Methods
In a pilot single-blinded, cross-over, randomised study, healthy subjects were fed for 4 weeks with ≥3-week washout between diets. Acute stress was induced via 100 mg intravenous corticotrophin-releasing hormone (CRH) on day 28 of each diet. Intestinal permeability was analysed directly with urinary lactulose to rhamnose ratio (LRR) before and at 2 weeks; fasting serum biomarkers reflecting barrier function (intestinal fatty acid binding protein, lipopolysaccharide binding protein [LBP], soluble CD14 and syndecan-1) were measured before and during each diet. All markers were also measured 2 h post CRH. Tolerance was assessed by gastrointestinal symptoms daily using a 100-mm visual analogue scale. Success of blinding was assessed by direct questioning and adherence (defined >95% consumption of only food provided) with food diaries.
Results
18 of 20 participants enrolled [median age: 34 IQR 23-46 y; 75% female] finished both diets. The diets were well tolerated with minimal overall symptoms (low: mean 9.9 (SD 8.3) vs high: 9.5 [5.5] mm). Adherence was excellent (>95%). Blinding was reasonable with 30% of participants either not knowing or choosing a high emulsifier diet as the therapeutic diet. In the unstressed state (Fig 1), LRR reduced on the HIGH diet compared to baseline (p=0.016), but no difference between diets was seen. LPB concentrations were lower in the HIGH than LOW diet (p=0.039). Under acute stress (Fig 2), LRR increased by 49% during the HIGH diet (p=0.034), but fell by 41% during the LOW diet (p=0.027). The paired CRH-induced LRR was reduced on LOW vs HIGH diet in acute stress (p=0.043). No difference in concentrations of other biomarkers were seen between diets.
Conclusion
Novel low and high emulsifier trial diets were well tolerated, achieved good adherence and reasonable blinding. Paradoxically, intestinal permeability reduced with the HIGH diet in the unstressed state, but the LOW diet protected from stress-induced increase in permeability. These diets are suitable to evaluate the effects of emulsifiers on intestinal permeability and inflammation in patients with CD.