Enteroids for Nutritional Studies

Abstract

Nutritional studies are greatly hampered by a paucity of proper models. Previous studies on nutrition have employed conventional cell lines and animal models to gain a better understanding of the field. These models lack certain correlations with human physiological responses, which impede their applications in this field. Enteroids are cultured from intestinal stem cells and include enterocytes, enteroendocrine cells, goblet cells, Paneth cells, and stem cells, which mimic hallmarks of in vivo epithelium and support long‐term culture without genetic or physiological changes. Enteroids have been used as models to study the effects of diet and nutrients on intestinal growth and development, ion and nutrient transport, secretory and absorption functions, the intestinal barrier, and location‐specific functions of the intestine. In this review, the existing models for nutritional studies are discussed and the importance of enteroids as a new model for nutritional studies is highlighted. Taken together, it is suggested that enteroids can serve as a potential model system to be exploited in nutritional studies.

Regulation of Enteroendocrine Cell Networks by the Major Human Gut Symbiont Bacteroides thetaiotaomicron

“…Our finding that epithelial cell monolayers generated from small intestinal crypts of GF mice do not accurately reflect the EEC makeup or response to Bt (with the exception of GIP + cells) and APS seen in vivo is at odds with their increasing use as a physiologic model of intestinal response to stimuli including microbes and nutrients ( Leushacke and Barker, 2014 ; Pearce et al, 2018 ; Yin et al, 2019 ). Our contradictory findings may relate to our use of GF mice, as SPF mice are the usual source of intestinal crypts ( Petersen et al, 2014 ; Roberts et al, 2019 ).…”

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

“…Since hiOs functionally mimic normal human gastrointestinal tract physiology and pathophysiology [151], they represent an effective platform to study human gastrointestinal functions and diseases [154] and are already being successfully employed to model epithelial barrier function [155,156], nutrient transport physiology during digestion [157], celiac disease [158], inflammatory bowel disease [159], and cancer [160][161][162][163]. hiOs provide unprecedented opportunities for the generation of in vitro systems with a sufficient level of complexity to model physiological and pathological diet-microbiome-host conditions [164,165] and pathogen-host interactions [72,155,[166][167][168][169][170][171][172][173][174][175]. Human microbiota suspensions, pathogenic organisms, and/or nutrients can indeed be microinjected into the pseudo-lumen of organoids, which can then be recovered and assayed for microbial composition, microbial transcriptomics, metabolites, and host gene expression profiles (Figure 1).…”

“…Epithelial organoids (enteroids and colonoids) have been employed to model the effects of diet and nutrients on intestinal growth and development, ion and nutrient transport, secretory and absorption functions, the intestinal barrier, and location-specific functions of the intestine [165]. hiOs responses to gut-microbiota metabolites and microbes could provide novel insights into the mechanisms by which those agents may prevent or trigger diseases, including infections, significantly extending our knowledge of diet-microbiome-host interactions [164].…”

“…The treatment of a human colonoid model with the probiotic Lactobacillus reuteri or its antimicrobial metabolite, reuterin, before or after challenge with S. typhimurium, reduced the adhesion, invasion, and intracellular survival of this pathogen compared to findings for untreated cells [187]. Since the isolation of fresh crypts that contain multipotent adult stem cells is invasive and there is limited availability of live primary human cells and tissues, organoids derived from mice have been often employed [165]. However, recent advancements in culturing protocols allow for generating both epithelial-mesenchymal organoids and epithelial region-specific intestinal organoids (enteroids or colonoids) from hiPSCs [150,152,188].…”

Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice

“…1,6 This model is excellently suited for investigations regarding ISCs and intestinal homeostasis. [7][8][9] Thus, the present study was conducted to verify the effects of uridine on ISCs and decipher the underlying molecular mechanism using the intestinal organoid model.…”