Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions

ABSTRACT The intestinal epithelium serves as a critical interface between the external environment and internal tissues, coordinating nutrient absorption, immune defense, and barrier integrity. Discerning the processes that maintain gut homeostasis has been challenging due to the complexity of the i...

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Main Author: J. M. Lemme-Dumit
Format: Article
Language:English
Published: American Society for Microbiology 2025-08-01
Series:mSphere
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Online Access:https://journals.asm.org/doi/10.1128/msphere.00820-24
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author J. M. Lemme-Dumit
author_facet J. M. Lemme-Dumit
author_sort J. M. Lemme-Dumit
collection DOAJ
description ABSTRACT The intestinal epithelium serves as a critical interface between the external environment and internal tissues, coordinating nutrient absorption, immune defense, and barrier integrity. Discerning the processes that maintain gut homeostasis has been challenging due to the complexity of the intestinal microenvironment and the difficulty in accessing human tissue. The advent of human intestinal organoid technology has transformed the field by providing relevant in vitro models that recapitulate the cellular diversity and function of the gut epithelium. A recent advance involves the integration of immune cells into organoid cultures, enabling the study of epithelial-immune cell interactions in both health and disease. Furthermore, the application of cutting-edge multi-omics approaches, including transcriptomics, proteomics, and metabolomics, has enabled a deeper understanding of intestinal cell signaling, niche factors, and host-microbe dynamics. These innovations have led to breakthroughs in translational research, particularly in the field of precision medicine. This minireview highlights how intestinal organoids derived from human tissue stem cells, coupled with high-resolution omics technologies, are advancing our knowledge of intestinal physiology, host responses, and disease mechanisms. It also describes the emergence of patient-derived organoids as tools to guide personalized therapeutic strategies for conditions such as inflammatory bowel disease and cystic fibrosis. As organoid models continue to evolve, the integration of additional tissue components—such as diverse immune cell lineages, stromal elements, vasculature, neural cells, and microbiota—will more accurately replicate the intricate nature of human physiology and broaden their translational potential.
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spelling doaj-art-a61de16ccdb544699dbc76368c989db22025-08-26T13:01:21ZengAmerican Society for MicrobiologymSphere2379-50422025-08-0110810.1128/msphere.00820-24Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactionsJ. M. Lemme-Dumit0Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USAABSTRACT The intestinal epithelium serves as a critical interface between the external environment and internal tissues, coordinating nutrient absorption, immune defense, and barrier integrity. Discerning the processes that maintain gut homeostasis has been challenging due to the complexity of the intestinal microenvironment and the difficulty in accessing human tissue. The advent of human intestinal organoid technology has transformed the field by providing relevant in vitro models that recapitulate the cellular diversity and function of the gut epithelium. A recent advance involves the integration of immune cells into organoid cultures, enabling the study of epithelial-immune cell interactions in both health and disease. Furthermore, the application of cutting-edge multi-omics approaches, including transcriptomics, proteomics, and metabolomics, has enabled a deeper understanding of intestinal cell signaling, niche factors, and host-microbe dynamics. These innovations have led to breakthroughs in translational research, particularly in the field of precision medicine. This minireview highlights how intestinal organoids derived from human tissue stem cells, coupled with high-resolution omics technologies, are advancing our knowledge of intestinal physiology, host responses, and disease mechanisms. It also describes the emergence of patient-derived organoids as tools to guide personalized therapeutic strategies for conditions such as inflammatory bowel disease and cystic fibrosis. As organoid models continue to evolve, the integration of additional tissue components—such as diverse immune cell lineages, stromal elements, vasculature, neural cells, and microbiota—will more accurately replicate the intricate nature of human physiology and broaden their translational potential.https://journals.asm.org/doi/10.1128/msphere.00820-24human intestinal modelorganoidsintestinal physiologyhost responsemulti-omicstranslational research
spellingShingle J. M. Lemme-Dumit
Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions
mSphere
human intestinal model
organoids
intestinal physiology
host response
multi-omics
translational research
title Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions
title_full Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions
title_fullStr Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions
title_full_unstemmed Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions
title_short Intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host-microbe interactions
title_sort intestinal organoid models as tools to interrogate the physiology of human mucosal tissues and host microbe interactions
topic human intestinal model
organoids
intestinal physiology
host response
multi-omics
translational research
url https://journals.asm.org/doi/10.1128/msphere.00820-24
work_keys_str_mv AT jmlemmedumit intestinalorganoidmodelsastoolstointerrogatethephysiologyofhumanmucosaltissuesandhostmicrobeinteractions