Abstract
Dietary fiber has been linked to improved gut health, yet the mechanisms behind this association remain poorly understood. One proposed mechanism is through its influence on the secretion of gut hormones, including glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). We aimed to: 1) investigate the impact of a fiber deficient diet on the intestinal morphological homeostasis; 2) evaluate L-cell secretion; and 3) to ascertain the role of GLP-1, GLP-2 and Takeda G protein-receptor-5 (TGR5) signaling in the response using GLP-1 receptor, GLP-2 receptor and TGR5 knockout mice. Female C57BL/6JRj mice (n = 8) either received a standard chow diet or were switched to a crude fiber-deficient diet for a short (21 days) and long (112 days) study period. Subsequent identical experiments were performed in GLP-1 receptor, GLP-2 receptor and TGR5 knockout mice. The removal of fiber from the diet for 21 days resulted in a decrease in small intestinal weight (p < 0.01) and a corresponding decrease in intestinal crypt depth in the duodenum, jejunum and ileum (p < 0.001, p < 0.05, and p < 0.01, respectively). Additionally, colon weight was decreased (p < 0.01). These changes were associated with a decrease in extractable GLP-1, GLP-2 and PYY in the colon (p < 0.05, p < 0.01, and p < 0.01). However, we could not show that the fiber-dependent size decrease was dependent on GLP-1 receptor, GLP-2 receptor or TGR5 signaling. Intestinal permeability was increased following the removal of fiber for 112 days. In conclusion, our study highlights the importance of dietary fiber to maintain intestinal weight, colonic L-cell secretion and intestinal integrity.
Highlights
Non-digestible carbohydrates, termed dietary fibers, have been linked to improved health outcome, especially concerning gut health [1]
We aimed to investigate the impact of a fiber deficient diet on the intestinal morphological homeostasis and L-cell secretion and to evaluate glucagon-like peptide-1 (GLP-1) receptor (GLP-1r), glucagon-like peptide-2 (GLP-2) receptor (GLP-2r) and Takeda G protein-receptor-5 (TGR5) signaling in the response using knockout mice
All knockout mice were bred by heterozygote breeding and GLP-1r+/+, GLP-2r+/+ and TGR5+/+ littermates were used as controls
Summary
Non-digestible carbohydrates, termed dietary fibers, have been linked to improved health outcome, especially concerning gut health [1] Their presence in the diet can delay gastric emptying rate [2], increase fecal bulk and moisture content [3], and impact bacterial diversity [4] and fermentation [5]. Intestinal Size, and L-Cell Secretion below the recommended guidelines [6] This ‘western diet’ is characterized by calorie-rich processed foods, high in sucrose and saturated fats with reduced dietary fiber [7] and is linked to the rise in noncommunicable diseases [1] and a decrease in microbial diversity [8, 9]. Together GLP-1 and GLP-2, synergistically ameliorate intestinal injury and improve intestinal healing [20]
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