Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn’s Disease

Abstract

G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn’s disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn’s disease patients and 10 colon cancer patients. The Crohn’s disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn’s disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn’s disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn’s disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn’s disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn’s disease patients in remission.

Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

“…This aspect was addressed in CD patients receiving DF supplementation to their enteral nutrition ( 143 ), which resulted in an increase in GPR43 + neutrophil infiltration when compared to enteral nutrition alone or patients in remission. Thus, prebiotics may be used to improve intestinal neutrophil recruitment.…”

Free Fatty Acid Receptors 2 and 3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View

“…Although FFAR2 expression is seen in brain parenchyma, comprehensive studies on its expression in the brain are needed to define its importance in brain functions [64]. FFAR2 expresses in hypothalamus [19], bone marrow [10,59], heart [68], liver [4,5,19], PBMC [35,[53][54][55][56]69], stomach [19], pancreatic islet β-cells [25], lungs [40], epidermal fat pads [4,19], white adipose tissue (WAT) including perirenal, epidermal, and subcutaneous tissues [22,26], ileum and colon [4,19] particularly intestinal epithelial cells (IECs) [28], L-cells [11], I-cells [3], K-cells [3] and Myeloid (M)-cells [70,71], cecum [72], and muscles [19] of mice. FFAR2 also express in the murine pancreatic β-cell line MIN6 [60,61,73] and adipocyte cell line 3T3-L1 [19,30,31,74,75].…”

“…Both the receptors are differentially expressed in the intestine [3,[10][11][12], adipose tissues [13,14], pancreas [15], bone marrow [10], liver [16,17], muscle [18,19], spleen [20,21], lungs [6,21,22], heart [23], and brain [17,24]. Widespread expression of FFAR2/3 make them play an important role in several human diseases such as type 1 and type 2 diabetes [11,[25][26][27][28][29], obesity [26,[30][31][32][33], inflammatory bowel disease (IBD) [34,35], Crohn's disease [36], cardiovascular diseases [20,37,38], gout [39], asthma [6,40,41], arthritis [35], and colitis [35,[42][43][44][45].…”

FFAR2/3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View

“…Both the receptors differentially expressed in intestine [2,[10][11][12], adipose tissues [13,14], pancreas [15], bone marrow [9], liver [16,17], muscle [18,19], spleen [20,21], lungs [5,20,21], heart [22] and brain [16,23]. Wide spread expression of FFAR2/3 make them to play an important role in several human diseases such as type-1 and -2 diabetes [10,[24][25][26][27][28], obesity [25,[29][30][31][32], inflammatory bowel disease (IBD) [33,34], Crohn`s disease [35], cardiovascular diseases [19,36,37], gout [38], asthma [5,39,40], arthritis [34], colitis [34,[41][42][43][44].…”