A pilot randomized controlled trial investigating the effects of an anti-inflammatory dietary pattern on disease activity, symptoms and microbiota profile in adults with inflammatory bowel disease

Inflammatory bowel disease (IBD) is increasingly prevalent, potentially linked to the adoption of Western dietary patterns high in ultra-processed foods and food additives. Current dietary guidelines for IBD are non-specific due to a lack of robust randomized controlled trials. The Mediterranean diet is known for its anti-inflammatory properties and beneficial effects on gut microbiota. Conversely, ultra-processed diets, often containing additives like artificial sweeteners and emulsifiers, have been associated with increased inflammation. This pilot study aimed to assess the safety, efficacy, and feasibility of an eight-week dietary intervention (IBD-MAID) designed to reduce exposure to pro-inflammatory components and food additives in adults with IBD, comparing it to general healthy eating advice.

Existing literature suggests a strong link between diet and IBD pathogenesis. The rise in IBD incidence mirrors the increased consumption of ultra-processed Western diets. Diet is a major lifestyle factor modified by IBD patients to manage symptoms, yet current guidelines lack specificity due to insufficient high-quality RCTs. The Mediterranean diet (TMD) is recognized for its anti-inflammatory effects and positive impact on gut microbiota diversity and abundance. In contrast, ultra-processed diets (UPDs) are correlated with higher inflammatory cytokines and oxidative stress markers. Studies using in vitro and animal models indicate that food additives damage the gut lining and disrupt the gut microbiome. However, the impact of these findings on IBD patients remains unclear.

This pilot randomized controlled trial (RCT) followed CONSORT guidelines. Over 16 weeks, adults (18-60 years) with established ulcerative colitis (UC) or Crohn's disease (CD), exhibiting worsening symptoms and fecal calprotectin (FC) >50 µg/mg, were recruited from IBD outpatient clinics. Participants were excluded based on various criteria including smoking status, pregnancy, allergies, ostomy, and recent medication changes. Participants were randomized 1:1 to either the Intervention group (IBD-MAID meals provided) or the Comparator group (general healthy eating advice). The Intervention group received two daily meals (lunch and dinner) for eight weeks, along with education on IBD-MAID principles. The Comparator group received general healthy eating advice via video. From weeks 8-16, the Comparator group transitioned to IBD-MAID education and provision of key ingredients. Primary outcome was change in disease activity (SCCAI for UC, CDAI for CD) from baseline to week 8. Secondary outcomes included quality of life (SIBDQ), symptoms (PRO2), FC, and C-reactive protein (CRP). Dietary adherence was assessed via 3-day food diaries, MEDAS score, and a food additive score. Statistical analysis included independent sample t-tests, ANCOVA, paired t-tests, and Spearman's correlation. Stool samples were collected for 16s rRNA sequencing and metagenomics analysis.

29 participants were randomized to each group. The IBD-MAID was well-tolerated (92% adherence). At week 8, there was no significant difference in disease activity between groups. However, within-group analysis showed significant improvements in the IBD-MAID group for symptoms (p=0.001), quality of life (p=0.004), FC (p=0.007), and Crohn's disease activity (p=0.03) from baseline to week 8. The Comparator group also showed a significant improvement in quality of life (p=0.015). Correlation analysis revealed a stronger decrease in food additive intake was associated with significant improvements in FC, symptoms, and quality of life. There was no significant difference in gut microbiome composition or abundance between groups.

The study findings suggest that while the IBD-MAID diet did not demonstrate superiority to general healthy eating advice in terms of overall disease activity after eight weeks, it did lead to significant improvements in symptoms, quality of life, and inflammatory markers within the intervention group. The lack of a significant difference between groups may be due to the improvement in dietary quality in both arms, as both diets emphasized increased consumption of fruits, vegetables, and whole grains. The most notable finding is the significant correlation between reduced food additive intake and improvements in inflammatory markers and patient-reported outcomes. This highlights the potential importance of minimizing food additive exposure in managing IBD. The lack of significant changes in gut microbiota may be due to insufficient power or the heterogeneity of the study population (including both UC and CD participants).

The IBD-MAID diet was well-tolerated and adhered to. While not superior to general healthy eating in overall disease activity, it showed significant within-group improvements in symptoms, quality of life, and inflammatory markers, particularly in Crohn's disease. A strong correlation between reduced food additive intake and improved outcomes was observed. Future research should focus on larger studies, specifically in UC, with more sensitive outcome measures and validated methods to quantify food additive intake to further explore the role of food additives in IBD pathogenesis and management. Development of tools to help individuals identify and reduce food additive consumption is also warranted.

This pilot study had a small sample size, limiting power to detect smaller effect sizes. The relatively mild disease severity at baseline in many participants might have limited the ability to detect significant changes in disease activity, particularly in UC. The eight-week intervention period might be insufficient to observe substantial changes in all outcome measures. The study lacked endoscopic assessment of mucosal healing, a key criterion for IBD treatment success. Challenges in recruiting participants with CD led to underpowered analysis in this subgroup. The study's reliance on self-reported dietary data introduces potential bias.