In this context, dietary fibers are the main energy source of the colonic microbiota, and in this way, they are critical food components shaping the gut microbiome. However, diet can also indirectly affect the ISCs responses, epithelial architecture, and intestinal inflammatory responses by its ability to modulate the gut microbial composition in the host, although the precise mechanisms behind such complex interactions are still not fully understood. ĭiet is an important environmental factor that strongly impacts the activity of ISCs and, therefore, the functionality of the gut, with most studies focusing on the caloric intake and energy metabolism properties of distinct dietary interventions to the intestinal stem cell niche. Thus, it is crucial to understand how distinct internal and external factors interact with the ISCs as any perturbation in this tightly regulated system can lead to dysfunction of this mucosal barrier and development of several pathologies. Gut protective barrier is also reinforced by the presence of immune cells, which can be organized in lymphoid tissues or be dispersed along the lamina propria and within the epithelium itself. Protective molecules are found embedded in the mucus layer, such as secretory IgA and antimicrobial peptides, the latter secreted by Paneth cells. In the small intestine, the barrier is a single layer of mucus, while in the colon, there are two layers-an inner that adheres strongly to the epithelium and an outer layer that is loosely attached and can be easily removed. This layer acts as a physical barrier between the epithelium and the digestive contents of the gut. Additionally, the intestinal epithelium is equipped with a protective mucus layer produced by goblet cells. Due to ISCs continuous proliferation, epithelial cells are in a constant upward movement, an important characteristic to assure tissue homeostasis. Intestinal stem cells (ISCs) located at the bottom of the crypts proliferate and differentiate into all mature cell types found in the epithelium: enterocytes and M cells (absorptive lineage), Paneth cells, goblet cells, Tuft cells, and enteroendocrine cells (secretory lineage). This dynamic structure made of a single layer of cells is built from crypt-villus units (with villi structures absent in the large intestine). The gut epithelium has the highest cellular turnover rate in adult mammals, which ensures that this large mucosal surface constantly regenerates to fulfill its barrier functions. Our study indicates complex cross kingdom and cross cell type interactions involved in the adaptation of the colon epithelium to the luminal environment in steady state. This study indicates that the intake of inulin affects the activity of intestinal stem cells and drives a homeostatic remodeling of the colon epithelium, an effect that requires the gut microbiota, γδ T cells, and the presence of IL-22. We also describe the pivotal role of γδ T lymphocytes and IL-22 in this microenvironment, as the inulin diet failed to induce epithelium remodeling in mice lacking this T cell population or cytokine, highlighting their importance in the diet-microbiota-epithelium-immune system crosstalk. This effect was dependent on the inulin-altered gut microbiota, as no modulations were observed in animals deprived of microbiota, nor in mice fed cellulose-enriched diets. We show that the consumption of inulin diet alters the colon epithelium by increasing the proliferation of intestinal stem cells, leading to deeper crypts and longer colons. Using a combination of histochemistry, host cell transcriptomics, 16S microbiome analysis, germ-free, gnotobiotic, and genetically modified mouse models, we analyzed the impact of inulin intake on the colonic epithelium, intestinal bacteria, and the local immune compartment. Mice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts intestinal stem cells functions, thus affecting the epithelial structure. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions.
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