Gastrointestinal epithelial innate immunity—regionalization and organoids as new model

Kayisoglu, Özge; Schlegel, Nicolas; Bartfeld, Sina

doi:10.1007/s00109-021-02043-9

Cited by 15 publications

(8 citation statements)

References 128 publications

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“…The epithelial cells of the proximal and distal SI have different genetic profiles that support specific regional nutrient absorption and digestion functions, as well as different immune defense requirements [ 27 , 28 , 29 , 30 ]. We previously showed that these two SI regions are differently affected by early life AB treatment at P20 [ 22 ]; thus in the present study, we analyzed adult proximal and distal SI separately.…”

Section: Resultsmentioning

confidence: 99%

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life

et al. 2022

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The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health effects. Here, we investigated whether AB-induced changes in the neonatal gut persisted up to adulthood and whether early life AB had additional long-term consequences for gut functioning. Mice received AB orally from postnatal day 10 to 20. Intestinal morphology, permeability, and gene and protein expression at 8 weeks were analyzed. Our data showed that the majority of the early life AB-induced gut effects did not persist into adulthood, yet early life AB did impact later life gut functioning. Specifically, the proximal small intestine (SI) of adult mice treated with AB in early life was characterized by hyperproliferative crypts, increased number of Paneth cells, and alterations in enteroendocrine cell-specific gene expression profiles. The distal SI of adult mice displayed a reduced expression of antibacterial defense markers. Together, our results suggest that early life AB leads to structural and physiological changes in the adult gut, which may contribute to disease development when homeostatic conditions are under challenge.

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Section: Resultsmentioning

confidence: 99%

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life

et al. 2022

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“…The organoid culture model has also helped in understanding the mechanisms of H. pylori-induced inflammation in both the innate and adaptive immune systems. Using murine embryo-derived organoids due to their sterility, Kayisoglu et al 54 reported that the expression pattern of Toll-like receptor 4 (TLR4) was independent of an interaction with gut microbiota, and was instead determined by developmental stage. Both the embryo-derived gastric organoids The ability of organoid cultures to replicate increased expression of inflammatory cytokines in response to H. pylori infection has been shown in both mucosoid cultures and 3D spheroid models.…”

Section: Application Of Organoids To Study Epithelial Interactions An...mentioning

confidence: 99%

Gastric organoids: Advancing the study of H. pylori pathogenesis and inflammation

2022

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For decades, traditional in vitro and in vivo models used for the study of Helicobacter pylori infection have relied heavily on the use of gastric cancer cell lines and rodents. Major challenges faced by these methods have been the inability to study cancer initiation in already cancerous cell lines, and the difficulty in translating results obtained in animal models due to genetic differences. These challenges have prevented a thorough understanding of the pathogenesis of disease and slowed the development of cancer therapies and a suitable vaccine against the pathogen. In recent years, the development of gastric organoids has provided great advantages over the traditional in vivo and in vitro models due to their similarities to the human stomach in vivo, their ease of use, and the capacity for long‐term culture. This review discusses the advantages and limitations of existing in vivo and in vitro models of H. pylori infection, and how gastric organoids have been applied to study H. pylori pathogenesis, with a focus on how the pathogen interacts with the gastric epithelium, inflammatory processes, epithelial repair, and cancer initiation. The potential applications of organoids to address more complex questions on the role of hormones, vaccine‐induced immunity are also discussed.

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“…Many challenges should be remained in the long-term culture, and the preservation of immune cells could be stocked, and then, they are reconstituted. Supplements such as IL-2, antibodies against CD3 or CD28 might improve the long-term maintenance of immune cells, but we need the novel recapitulation of antitumor response by these combined organoids would be certainly necessary for robust validation [ 69 , 70 ].…”

Section: Hgo Applicationmentioning

confidence: 99%

Translational models of 3-D organoids and cancer stem cells in gastric cancer research

Wuputra

Kato

et al. 2021

Stem Cell Res Ther

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It is postulated as a general concept of cancer stem cells (CSCs) that they can produce cancer cells overtly and repopulate cancer progenitor cells indefinitely. The CSC niche is part of a specialized cancer microenvironment that is important to keep the phenotypes of CSCs. Stem cell- and induced pluripotent stem cell (iPSC)-derived organoids with genetic manipulation are beneficial to the investigation of the regulation of the microenvironment of CSCs. It would be useful to assess the efficiency of the cancer microenvironment on initiation and progression of cancers. To identify CSCs in cancer tissues, normal cell organoids and gastric cancer organoids from the cancerous areas, as well as iPSCs, were established several years ago. However, many questions remain about the extent to which these cultures recapitulate the development of the gastrointestinal tract and the mechanism of Helicobacter pylori-induced cancer progression. To clarify the fidelity of human organoid models, we have noted several key issues for the cultivation of, and differences between, normal and cancerous organoids. We developed precise culture conditions for gastric organoids in vitro to improve the accuracy of the generation of organoid models for therapeutic and medical applications. In addition, the current knowledge on gastrointestinal CSC research, including the topic of CSC markers, cancer cell reprogramming, and application to target cancer cell plasticity through niches, should be reinforced. We discuss the progression of cancers derived from human gastric organoids and the identification of CSCs.

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Gastrointestinal epithelial innate immunity—regionalization and organoids as new model

Cited by 15 publications

References 128 publications

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life

Gastric organoids: Advancing the study of H. pylori pathogenesis and inflammation

Translational models of 3-D organoids and cancer stem cells in gastric cancer research

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