Metaproteomics reveals altered gut microbiota and differential responses to diet intervention in Crohn's disease patients according to disease location

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) that causes chronic mucosal inflammation in different regions of the gastrointestinal tract, due to genetic and environmental factors. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients has not been carefully studied so far. In this work, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on the GM function in CD patients.

CD patients were divided in three main groups. The first one (Group 1, n=10) followed a Mi-IBD diet after a one-time diet counseling. The second one (Group 2, n=16) received catered food for 8 weeks while the third one (Group 3, n=22 dyads) received catered food for 8 weeks for a CD patient and a healthy household control (HHC). Group 3 patients and HHCs also participated in Dyadic Psychosocial Support (DPS) sessions. Stool samples were collected at baseline, week 8, and week 36 and analyzed by liquid chromatography-tandem mass spectrometry.

Results showed a high heterogeneity between patients, groups of subjects and across the time points, making quite challenging the identification of a modulation of the GM functionality prompted by the diet. Diet-induced changes involving the activation of bacterial metabolic pathways were observed, including those related to carbohydrate metabolism due to an increased fiber uptake. Interestingly, the activity of taxa accomplishing such functions was affected by the inflamed environment and the microbial composition underlying the metaproteomic changes differed between patients with ileal only disease or with colonic involvement.

The Mi-IBD diet changed the microbial function of both CD patients and HHC. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Comparing the effect of a diet intervention between diverse CD patients and HHCs provided additional insight into diet optimization to achieve defined salutary functions.