A LOW FAT, HIGH FIBER DIETARY INTERVENTION IN CROHN’S DISEASE (CD) PATIENTS IMPROVES SERUM PROTEOMIC AND METABOLOMIC PATTERNS REFLECTING IMPROVEMENTS IN SYSTEMIC INFLAMMATION AND MUCOSAL HEALING

Background: Crohn’s disease (CD) is characterized by chronic intestinal inflammation and dysbiosis. Diet plays a pivotal role in the development of CD and recent studies highlight the feasibility and effectiveness of specific diet interventions in improving symptoms. However, little is known about the degree to which diet-modulation impacts host-microbiome dynamics and biological responses in CD. To address this gap, we conducted a patient preference study, examining the effects of a catered low-fat, high-fiber (LF/HF) diet on symptoms, circulating protein levels, and fecal metabolomics in CD patients and healthy household controls (HHC) receiving identical diets.
Methods: In our study (NCT04213729), 73 patients and 24 HHC participated, choosing between diet counseling alone (group 1), 8 weeks of catered food (group 2), or catered food with dyadic psychosocial support (DPS) for the patient and a HHC (group 3). Data on demographics, clinical parameters, quality of life, and food knowledge along with fecal and serum samples were collected at baseline and week 8. Proteomic analysis was done using SOMAscan assay, and metabolomics analysis was done by liquid chromatography–mass spectrometry global analysis. Biological pathway and network analyses were performed.
Results: Baseline analysis indicated that CD patients had a diet lower in fiber and higher in fat, and a lower healthy eating index (HEI) compared to HHC and the average U.S. population. Proteomic analysis showed elevated pro-inflammatory and immune-modulatory proteins (eg- SAA1, CRP, IgA, etc.) in CD patients, along with reduced TCN2 and ADH1C compared to HHC. Catering meals resulted in short-term adherence and significant improvements in macronutrient profile, food related quality of life, and patient reported symptoms as measured by short Crohn’s Disease Activity Index (scDAI) for groups 2 and 3 but not group 1. At the 8-week mark, CD patients had a marked decrease in pro-inflammatory and lipid markers (eg- CRP, leptin, etc) and an upregulation in ADH1C, Rab-21 and Rab-7. Pathway analysis revealed an enrichment in pathways associated with amino acid and fatty acid metabolism and endothelial cell development at the 8-week timepoint in CD patients. Stool metabolomics revealed a marked separation in the metabolome of the catered-diet groups compared to Group 1. A summary of modulated proteins and pathways is provided in Figure 1.
Conclusion: Our results suggest that CD patients eating a carefully designed and catered LF/HF diet for 8 weeks have changes in their serum proteome that reflect an improvement in systemic inflammation and pathways involved in mucosal healing. Our data show that a carefully controlled diet even for 8 weeks is enough to improve immune function, mucosal healing, and inflammatory status. These strategies can lead to identification of novel targets of diet responses in CD.