Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

Abstract

Background 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. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. 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. 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. Methods Mice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. 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. Results 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. 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 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. Conclusion 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. 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.

Effects of Intestinal Microbiota on the Biological Transformation of Arsenic in Zebrafish: Contribution and Mechanism

“…They form mutually beneficial symbiotic complexes through coevolution between each other. For instance, gut microbiome can remodel the homeostasis of colon epithelium after intake of dietary soluble fibers and maintain the gut–epithelial barrier and its functions . It can also regulate the host metabolism by influencing metabolic inflammation, serum lipopolysaccharides, intestinal barrier function, and other physiological functions. − In this study, in as3mt –/– zebrafish, both microbial richness and structure were more significantly correlated with arsenicals (including tAs and iAs).…”

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer’s disease in mice

“…The impact of SCFAs or other inulin-derived metabolites on astrocyte CXCL12 expression is unknown. The anti-inflammatory effects of inulin-derived metabolites may also include gut epithelial remodeling [111], induction of regulatory ILC2s in the gut [35], and protection via brain T regs . The protection conferred by inulin in the gut is also predicted to attenuate systemic inflammation driven by leaky gut antigens [111].…”

“…The anti-inflammatory effects of inulin-derived metabolites may also include gut epithelial remodeling [111], induction of regulatory ILC2s in the gut [35], and protection via brain T regs . The protection conferred by inulin in the gut is also predicted to attenuate systemic inflammation driven by leaky gut antigens [111]. Overall, the inulin diet likely rescued against AD hallmarks via multiple mechanisms acting on the gut, the brain, and peripheral immune cells.…”

The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity

“…When it comes to the different types of fibers, they can be categorized by fermentability, solubility and viscosity. Due to the fermentability of β-glucans, pectins and inulin, these fibers mainly promote systemic health via gut microbiota modulation ( 65 ) whereas non-fermentable fibers like psyllium, which has a high solubility and viscosity, independently improve digestion, glucose homeostasis and cholesterol levels ( 60 ). Due to the differently mediated benefits of various kinds of fibers, a plant-based diet comprising different types of dietary fibers is recommended.…”