The role of goblet cells and mucus in intestinal homeostasis

Gustafsson, Jenny; Johansson, Malin

doi:10.1038/s41575-022-00675-x

Cited by 254 publications

(139 citation statements)

References 236 publications

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“…Epithelial permeability barrier is mainly regulated by the tight junctions which consist of intracellular and apical intercellular membrane proteins, including zonula occludens (ZO), claudins and occluding [ 3 , 4 , 5 ], which regulate epithelial leakiness by selectively modulating ion and pore size of the intestinal epithelium [ 5 ]. Specialized epithelial cell types such as goblet cells and Paneth cells could also support intestinal barrier function by providing protective mucous layer and secreting antimicrobial peptides [ 6 , 7 ]. Weaning stress induces intestinal barrier dysfunctions, including defects of intestinal epithelial junction, decreased thickness of mucosal layer, and defective production of antimicrobial peptides [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Co-Cultures of Lactobacillus acidophilus and Bacillus subtilis Enhance Mucosal Barrier by Modulating Gut Microbiota-Derived Short-Chain Fatty Acids

Xie

Qian

et al. 2022

Nutrients

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Weaning stress induces intestinal barrier dysfunction and immune dysregulation in mammals. Various interventions based on the modulation of intestinal microbiota have been proposed. Our study aims to explore the effects of co-cultures from Lactobacillus acidophilus and Bacillus subtilis (FAM®) on intestinal mucosal barrier from the perspective of metabolic function of gut microbiota. A total of 180 piglets were allocated to three groups, i.e., a control group (C, basal diet), a FAM group (F, basal diet supplemented with 0.1% FAM), and an antibiotic group (A, basal diet supplemented with antibiotic mixtures). Here, we showed FAM supplementation significantly increased body weight and reduced diarrhea incidence, accompanied by attenuated mucosal damage, increased levels of tight junction proteins, serum diamine oxidase (DAO) and antimicrobial peptides. In addition, 16S rRNA sequencing and metabolomic analysis revealed an increase in relative abundance of Clostridiales, Ruminococcaceae, Firmicutes and Muribaculaceae and a significant increase in the total short-chain fatty acids (SCFAs) and butyric acid in FAM-treated piglets. FAM also increased CD4+ T cells and SIgA+ cells in intestinal mucosa and SIgA production in colon contents. Furthermore, FAM upregulated the expression of IL-22, short-chain fatty acid receptors GPR43 and GPR41, aryl hydrocarbon receptor (AhR), and hypoxia-inducible factor 1α (HIF-1α). FAM shows great application prospect in gut health and provides a reference for infant weaning.

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Section: Introductionmentioning

confidence: 99%

Co-Cultures of Lactobacillus acidophilus and Bacillus subtilis Enhance Mucosal Barrier by Modulating Gut Microbiota-Derived Short-Chain Fatty Acids

Xie

Qian

et al. 2022

Nutrients

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“…We hypothesized that these novel structures were caused by an uptake of luminal extracellular contents. Indeed, such a process has been demonstrated in intestinal secretory/goblet cells (Gustafsson et al, 2021; Gustafsson & Johansson, 2022; McDole et al, 2012; Noah et al, 2019). To definitely evaluate our hypothesis concerning the origin of the spherical autofluorescence “voids” in our system, we added 10kd FITC-dextran to the extracellular fluid.…”

Section: Resultsmentioning

confidence: 98%

“…We also use live autofluorescence imaging to reveal the existence of secretory cell associated antigen passages (SAPs) in the airway. The biology of such structures has only recently been dissected in the gut where they have been termed goblet cell associated antigen passages (GAPs) (Gustafsson et al, 2021; Gustafsson & Johansson, 2022; Knoop et al, 2014; McDole et al, 2012; Noah et al, 2019). Furthermore, we describe the real time dynamics of the formation of these structures for the first time using physiologic cholinergic stimulation of airway explants.…”

Section: Introductionmentioning

confidence: 99%

Label free autofluorescence imaging permits comprehensive and simultaneous assignment of cell type identity and reveals the existence of airway secretory cell associated antigen passages (SAPs)

Shah

Hou

Vinarsky

et al. 2022

Preprint

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The specific functional properties of a tissue are distributed amongst its component cell types. The various cells act coherently, as an ensemble, in order to execute a properly orchestrated physiologic response. Thus, modern approaches to dissect physiologic mechanism would benefit from an ability to identify specific cell types in live tissues and image them in real time. Current techniques require the use of fluorescent genetic reporters that are not only cumbersome, but which only allow the simultaneous study of 2 or 3 cell types. We report a non-invasive imaging modality that capitalizes on the endogenous autofluorescence signatures of the metabolic cofactors NAD(P)H and FAD. By marrying morphological characteristics with autofluorescence signatures, all seven of the airway epithelial cell types can be distinguished simultaneously in real time. Furthermore, we find that this methodology for direct cell type specific identification avoid potential pitfalls with the use of ostensibly cell type-specific markers that can be altered by clinically relevant physiologic stimuli. Finally, we utilize this methodology to interrogate realtime physiology using a clinically relevant model of cholinergic stimulation and identify dynamic secretory cell associated antigen passages (SAPs) that are highly reminiscent of previously reported goblet cell associated antigen passages (GAPs) in the intestine.

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“…In addition, GCs participate in the immune response through non-specific endocytosis and a pathway called the goblet-cell-associated antigen passages (GAPs) [ 141 , 142 , 143 ]. It is now believed that these cells not only form mucus but are also closely related to the immune system [ 143 , 144 ]. The proportion of GCs to other IECs increases from the duodenum (4%) to distal colon (16%), in proportion to the number of microorganisms residing in these intestinal segments [ 107 , 109 ].…”

Section: Autophagy In Normal Large Intestine Epithelial Cells—implica...mentioning

confidence: 99%

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

Kasprzak

2023

IJMS

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Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Along with apoptosis and inflammation, autophagy is one of three important mechanisms in CRC. The presence of autophagy/mitophagy in most normal mature intestinal epithelial cells has been confirmed, where it has mainly protective functions against reactive oxygen species (ROS)-induced DNA and protein damage. Autophagy regulates cell proliferation, metabolism, differentiation, secretion of mucins and/or anti-microbial peptides. Abnormal autophagy in intestinal epithelial cells leads to dysbiosis, a decline in local immunity and a decrease in cell secretory function. The insulin-like growth factor (IGF) signaling pathway plays an important role in colorectal carcinogenesis. This is evidenced by the biological activities of IGFs (IGF-1 and IGF-2), IGF-1 receptor type 1 (IGF-1R) and IGF-binding proteins (IGF BPs), which have been reported to regulate cell survival, proliferation, differentiation and apoptosis. Defects in autophagy are found in patients with metabolic syndrome (MetS), inflammatory bowel diseases (IBD) and CRC. In neoplastic cells, the IGF system modulates the autophagy process bidirectionally. In the current era of improving CRC therapies, it seems important to investigate the exact mechanisms not only of apoptosis, but also of autophagy in different populations of tumor microenvironment (TME) cells. The role of the IGF system in autophagy in normal as well as transformed colorectal cells still seems poorly understood. Hence, the aim of the review was to summarize the latest knowledge on the role of the IGF system in the molecular mechanisms of autophagy in the normal colon mucosa and in CRC, taking into account the cellular heterogeneity of the colonic and rectal epithelium.

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The role of goblet cells and mucus in intestinal homeostasis

Cited by 254 publications

References 236 publications

Co-Cultures of Lactobacillus acidophilus and Bacillus subtilis Enhance Mucosal Barrier by Modulating Gut Microbiota-Derived Short-Chain Fatty Acids

Co-Cultures of Lactobacillus acidophilus and Bacillus subtilis Enhance Mucosal Barrier by Modulating Gut Microbiota-Derived Short-Chain Fatty Acids

Label free autofluorescence imaging permits comprehensive and simultaneous assignment of cell type identity and reveals the existence of airway secretory cell associated antigen passages (SAPs)

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

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