Maturation of human intestinal organoids in vitro facilitates colonization by commensal lactobacilli by reinforcing the mucus layer

Son, Ye Seul; Ki, Soo Jin; Rajangam, Thanavel; Kim, Jong-Jin; Lee, Mi‐Ok; Kim, Jang Hwan; Jung, Cho‐Rok; Han, Tae-Su; Cho, Hyun Soo; Ryu, Choong-Min; Kim, Sang‐Heon; Park, Doo-Sang; Son, Mi‐Young

doi:10.1096/fj.202000063r

Cited by 33 publications

(25 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that butyrate could upregulate the expression of MUC2 and MUC5A, increase the epithelial barrier function, induce the assembly of tight junctions and enhance the glycosylation of mucus in Caco-2 and HT-29 cells (Gaudier et al, 2004;Peng et al, 2009;Nielsen et al, 2018). Probiotics-derived short-chain fatty acids(SCFAs) could regulate epithelial barrier, promote mucus release, and induce differentiation of intestinal epithelial cells (Son et al, 2020). The bioactive components secreted by probiotic bacteria could also contribute to the expression of mucins and changes in O-glycosylation of mucins (Da Silva et al, 2014;Wang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the mucus is also the first barrier protecting the gut from being invaded by the bacteria. Mucus is critical for the intestinal health since disruption of this boundary will probably result in bacterial penetration of mucus barrier and induce intestinal inflammation (Liu et al, 2020;Sharma et al, 2020;Son et al, 2020). It has been reported that gut bacteria could colonize the intestinal mucus layer in vivo and adhere to HT-29 cell in vitro (Altamimi et al, 2016;Engevik et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Lu²,

Mao

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

C. butyricum is a common gut commensal bacterium, which has many positive functions in human intestine. In this study, we investigated the effects of monosaccharide and its derivatives on the adhesion of C. butyricum to the mucus of HT-29 cells. RNA interference was performed to assess the roles of MUC2 and glycan in the adhesion of C. butyricum to HT-29 cells. The effects of C. butyricum on the glycosylation of mucins were assayed with fluorescence microscope. The expression levels of mucins and glycotransferases were also determined. The results showed that C. butyricum could adhere to the mucins secreted by HT-29 cells. Several kinds of monosaccharides inhibited the adhesion of C. butyricum to HT-29 cells, which suggested that the mucus glycan was the attaching sites of this bacterium. Knockdown of MUC2, FUT2 or GALNT7 significantly decreased the numbers of the bacteria adhering to HT-29 cells. When colonizing on the surface of HT-29 cells, C. butyricum could increase the production of mucins, promote the expression of glycotransferase, and induce the glycosylation of mucins. These results demonstrated that the glycan of mucus played important roles in the adhesion of C. butyricum to HT-29 cells. This study indicates for the first time that C. butyricum possesses the ability to modulate the glycosylation profile of mucus secreted by HT-29 cells. These findings contribute to understanding the mechanism of interaction between colonic epithelial cells and commensal bacteria.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Lu²,

Mao

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Compared to co-culture with human cells, crosstalk with the microbial community in an in vitro model is much more challenging. Several models, including Transwell inserts [ 109 ], intestinal organoids [ 110 ], and specialized bioreactor models [ 111 ], were tested to sustain complex populations of human intestinal microbiota in contact with living human tissues to mimic physiologically and pathologically related human intestine-microbiome crosstalk. In Transwell models, co-culture with bacteria could only be carried out within hours, due to the uncontrolled overgrowth of bacteria [ 112 ].…”

Section: Current Intestine Modelsmentioning

confidence: 99%

Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip

Chen

Zhao

et al. 2021

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Intestinal dysfunction is frequently driven by abnormalities of specific genes, microbiota, or microenvironmental factors, which usually differ across individuals, as do intestinal physiology and pathology. Therefore, it’s necessary to develop personalized therapeutic strategies, which are currently limited by the lack of a simulated intestine model. The mature human intestinal mucosa is covered by a single layer of columnar epithelial cells that are derived from intestinal stem cells (ISCs). The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments. However, a simulated intestine model will serve as an indispensable foundation for personalized drug screening. In this article, we review the advantages and disadvantages of conventional 2-dimensional models, intestinal organoid models, and current microfluidic intestine-on-a-chip (IOAC) models. The main technological strategies are summarized, and an advanced microfluidic primary IOAC model is proposed for personalized intestinal medicine. In this model, primary ISCs and the microbiome are isolated from individuals and co-cultured in a multi-channel microfluidic chip to establish a microengineered intestine device. The device can faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions. Moreover, the ISCs can be genetically edited before seeding, and monitoring sensors and post-analysis abilities can also be incorporated into the device to achieve high-throughput and rapid pharmaceutical studies. We also discuss the potential future applications and challenges of the microfluidic platform. The development of cell biology, biomaterials, and tissue engineering will drive the advancement of the simulated intestine, making a significant contribution to personalized medicine in the future. Graphical abstract The intestine is a primary organ for digestion, absorption, and metabolism, as well as a major site for the host-commensal microbiota interaction and mucosal immunity. The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments, though physiological 3-dimensional of the native small intestinal epithelial tissue has been well documented. An intestinal stem cells-based microfluidic intestine-on-a-chip model that faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions will make a significant contribution.

show abstract

“…It has also been demonstrated that lactobacilli are capable of exerting a modulating effect on the host's immune system. However, epithelial-commensal bacterial interactions with the host organism have been hardly studied due to limited access to the tissues of the human small intestine (Son et al 2020). Some lactobacilli species have developed the ability to stimulate the generation of reactive oxygen species (ROS) in epithelial cells, which leads to the proliferation of intestinal epithelial cells through processes requiring the catalytic action of Nox1.…”

Section: Using Organoids To Model Infectious Diseases and Study Adaptmentioning

confidence: 99%

3D organotypic cell structures for drug development and Microorganism-Host interaction research

Zubareva¹,

Nadezhdin²,

Nadezhdina³

et al. 2021

RRP

View full text Add to dashboard Cite

Introduction: The article describes a new method of tissue engineering, which is based on the use of three-dimensional multicellular constructs consisting of stem cells that mimic the native tissue in vivo – organoids. 3D cell cultures: The currently existing model systems of three-dimensional cultures are described. Characteristics of organoids and strategies for their culturing: The main approaches to the fabrication of 3D cell constructs using pluripotent (embryonic and induced) stem cells or adult stem cells are described. Brain organoids (Cerebral organoids): Organoids of the brain, which are used to study the development of the human brain, are characterized, with the description of biology of generating region-specific cerebral organoids. Lung organoids: Approaches to the generation of lung organoids are described, by means of pluripotent stem cells and lung tissue cell lines. Liver organoids: The features of differentiation of stem cells into hepatocyte-like cells and the creation of 3D hepatic organoids are characterized. Intestinal organoids: The formation of small intestine organoids from stem cells is described. Osteochondral organoids: Fabrication of osteochondral organoids is characterised. Use of organoids as test systems for drugs screening: The information on drug screening using organoids is provided. Using organoids to model infectious diseases and study adaptive responses of microorganisms when interacting with the host: The use of organoids for modeling infectious diseases and studying the adaptive responses of microorganisms when interacting with the host organism is described. Conclusion: The creation of three-dimensional cell structures that reproduce the structural and functional characteristics of tissue in vivo, makes it possible to study the biology of the body’s development, the features of intercellular interactions, screening drugs and co-cultivating with viruses, bacteria and parasites.

show abstract

Maturation of human intestinal organoids in vitro facilitates colonization by commensal lactobacilli by reinforcing the mucus layer

Cited by 33 publications

References 61 publications

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip

3D organotypic cell structures for drug development and Microorganism-Host interaction research

Contact Info

Product

Resources

About