scholarly journals In Vitro Reconstitution of an Intestinal Mucus Layer Shows That Cations and pH Control the Pore Structure That Regulates Its Permeability and Barrier Function

2020 ◽  
Vol 3 (5) ◽  
pp. 2897-2909 ◽  
Author(s):  
Abhinav Sharma ◽  
Jun-Goo Kwak ◽  
Kristopher W. Kolewe ◽  
Jessica D. Schiffman ◽  
Neil S. Forbes ◽  
...  
Keyword(s):  
Pore Structure ◽  
Barrier Function ◽  
Ph Control ◽  
Mucus Layer ◽  
Intestinal Mucus ◽  
In Vitro Reconstitution ◽  
Intestinal Mucus Layer

scholarly journals Bifidobacterium dentiumFortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Melinda A. Engevik ◽  
Berkley Luk ◽  
Alexandra L. Chang-Graham ◽  
Anne Hall ◽  
Beatrice Herrmann ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathways ◽  
Goblet Cell ◽  
Cell Function ◽  
Goblet Cells ◽  
Mucus Layer ◽  
Content Type ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

ABSTRACTMuch remains unknown about how the intestinal microbiome interfaces with the protective intestinal mucus layer.Bifidobacteriumspecies colonize the intestinal mucus layer and can modulate mucus production by goblet cells. However, selectBifidobacteriumstrains can also degrade protective glycans on mucin proteins. We hypothesized that the human-derived speciesBifidobacterium dentiumwould increase intestinal mucus synthesis and expulsion, without extensive degradation of mucin glycans.In silicodata revealed thatB. dentiumlacked the enzymes necessary to extensively degrade mucin glycans. This finding was confirmed by demonstrating thatB. dentiumcould not use naive mucin glycans as primary carbon sourcesin vitro. To examineB. dentiummucus modulationin vivo, Swiss Webster germfree mice were monoassociated with live or heat-killedB. dentium. LiveB. dentium-monoassociated mice exhibited increased colonic expression of goblet cell markersKrüppel-like factor 4(Klf4),Trefoil factor 3(Tff3),Relm-β,Muc2, and several glycosyltransferases compared to both heat-killedB. dentiumand germfree counterparts. Likewise, liveB. dentium-monoassociated colon had increased acidic mucin-filled goblet cells, as denoted by Periodic Acid-Schiff-Alcian Blue (PAS-AB) staining and MUC2 immunostaining.In vitro,B. dentium-secreted products, including acetate, were able to increase MUC2 levels in T84 cells. We also identified thatB. dentium-secreted products, such as γ-aminobutyric acid (GABA), stimulated autophagy-mediated calcium signaling and MUC2 release. This work illustrates thatB. dentiumis capable of enhancing the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways, with a net increase in mucin production.IMPORTANCEMicrobe-host interactions in the intestine occur along the mucus-covered epithelium. In the gastrointestinal tract, mucus is composed of glycan-covered proteins, or mucins, which are secreted by goblet cells to form a protective gel-like structure above the epithelium. Low levels of mucin or alterations in mucin glycans are associated with inflammation and colitis in mice and humans. Although current literature links microbes to the modulation of goblet cells and mucins, the molecular pathways involved are not yet fully understood. Using a combination of gnotobiotic mice and mucus-secreting cell lines, we have identified a human-derived microbe,Bifidobacterium dentium, which adheres to intestinal mucus and secretes metabolites that upregulate the major mucin MUC2 and modulate goblet cell function. Unlike otherBifidobacteriumspecies,B. dentiumdoes not extensively degrade mucin glycans and cannot grow on mucin alone. This work points to the potential of usingB. dentiumand similar mucin-friendly microbes as therapeutic agents for intestinal disorders with disruptions in the mucus barrier.

P071 MODULATION OF THE MUCUS LAYER BY BIFIDOBACTERIUM DENTIUM PROVIDES PROTECTION IN A MODEL OF COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Melinda Engevik ◽  
Wenly Ruan ◽  
Faith Ihekweazu ◽  
James Versalovic
Keyword(s):  
Goblet Cell ◽  
Molecular Mechanisms ◽  
Goblet Cells ◽  
Mucus Layer ◽  
Mucin Production ◽  
Germ Free ◽  
Positive Effects ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

Abstract Background The intestinal mucus layer serves as a critical interface between the environment and the host. Patients with inflammatory bowel disease (IBD), particularly ulcerative colitis, exhibit reduced synthesis and secretion of the mucus protein MUC2 and decreased mucus thickness. This in turn promotes immune activation and inflammation. The clinical relevance of the mucus layer emphasizes the need to address strategies to modulate this barrier. Although bifidobacteria represent only 3–6% of the healthy adult fecal microbiota, their presence has been associated with numerous health benefits, including bolstering mucus production. However, the molecular mechanisms that underlie these positive effects appear to be strain-specific and are not well defined. We hypothesized that the human-derived Bifidobacterium dentium would increase intestinal mucus synthesis and expulsion via specific metabolites. We also speculated that modulation of goblet cells would be beneficial during colitis. Methods & Results In silico genome analysis revealed that B. dentium lacked the enzymatic repertoire required for degradation of mucin glycans. Consistent with these findings, we found that B. dentium could not use mucin glycans as a primary carbon source in vitro. To examine mucus modulation in vivo, germ-free mice were mono-associated with live or heat-killed B. dentium. Live B. dentium mono-associated mice exhibited increased colonic expression of goblet cell markers Krüppel-Like Factor 4 (Klf4), Relmβ, trefoil factor 3 (Tff3), Muc2, and several mucin glycosyltransferases compared to both heat-killed B. dentium and germ-free counterparts. Likewise, live B. dentium mono-associated colon had increased acidic mucin-filled goblet cells as denoted by MUC2 and PAS-AB staining. In vitro, B. dentium secreted products, including acetate, were able to increase MUC2 levels in T84 cells, mouse colonoids and human colonoids. We also identified that B. dentium secreted products, such as GABA, stimulated autophagy-mediated calcium signaling and MUC2 release. To identify whether B. dentium could enhance MUC2 production in mice harboring a complete microbiota, specific pathogen free mice were treated with live B. dentium by oral gavage. Administration of B. dentium increased the inner mucus layer compared to controls. Moreover, in a TNBS model of colitis, B. dentium treated mice had increased goblet cell numbers and MUC2 mRNA. Mirroring these findings, B. dentium treated mice lost less weight, had improved histology and had decreased levels of TNF, KC (IL-8), and IL-6. Conclusions This work illustrates that B. dentium enhances the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways with a net increase in mucin production. Ultimately, these pathways may be targeted for the development of novel therapeutics.

scholarly journals Oxyresveratrol Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats by Suppressing Inflammation

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2630
Author(s):  
Jiah Yeom ◽  
Seongho Ma ◽  
Jeong-Keun Kim ◽  
Young-Hee Lim
Keyword(s):  
Inflammatory Cytokine ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Mucus Layer ◽  
Beneficial Effects ◽  
Intestinal Mucus ◽  
Anti Inflammatory ◽  
Apoptotic Effects ◽  
Intestinal Mucus Layer

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.

scholarly journals Intestinal Mucus Layer Preservation in Female Rats Attenuates Gut Injury After Trauma-Hemorrhagic Shock

2010 ◽  
Vol 68 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Sharvil U. Sheth ◽  
Qi Lu ◽  
Kate Twelker ◽  
Susan M. Sharpe ◽  
Xiaofa Qin ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Female Rats ◽  
Mucus Layer ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

scholarly journals The fate of cellulose nanocrystal stabilised emulsions after simulated gastrointestinal digestion and exposure to intestinal mucosa

Nanoscale ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 2991-2998 ◽  
Author(s):  
Alan Mackie ◽  
Simon Gourcy ◽  
Neil Rigby ◽  
Jonathan Moffat ◽  
Isabel Capron ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Cellulose Nanocrystals ◽  
Cellulose Nanocrystal ◽  
Mucus Layer ◽  
Gastrointestinal Digestion ◽  
Simulated Gastrointestinal Digestion ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

The intestinal mucus layer prevents cellulose nanocrystals from reaching the epithelium and can modulate lipid and bile absorption.

The Intestinal Mucus Layer Comes of Age

2016 ◽  
Vol 37 (1) ◽  
pp. 3-4 ◽  
Author(s):  
Shipra Vaishnava
Keyword(s):  
Mucus Layer ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

scholarly journals Characterization of increased mucus production of HT29-MTX-E12 cells grown under Semi-Wet interface with Mechanical Stimulation

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261191
Author(s):  
Janneke Elzinga ◽  
Benthe van der Lugt ◽  
Clara Belzer ◽  
Wilma T. Steegenga
Keyword(s):  
Cell Line ◽  
Mechanical Stimulation ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Intestinal Cell ◽  
Mucus Layer ◽  
Mucus Production ◽  
Intestinal Mucus ◽  
Cells Cultured

The intestinal mucus layer plays a crucial role in human health. To study intestinal mucus function and structure in vitro, the mucus-producing intestinal cell line HT29-MTX-E12 has been commonly used. However, this cell line produces only low amounts of the intestine-specific MUC2. It has been shown previously that HT29-MTX-E12 cells cultured under Semi-Wet interface with Mechanical Stimulation (SWMS) produced higher amounts of MUC2, concomitant with a thicker mucus layer, compared to cells cultured conventionally. However, it remains unknown which underlying pathways are involved. Therefore, we aimed to further explore the cellular processes underlying the increased MUC2 production by HT29-MTX-E12 cells grown under SWMS conditions. Cells grown on Transwell membranes for 14 days under static and SWMS conditions (after cell seeding and attachment) were subjected to transcriptome analysis to investigate underlying molecular pathways at gene expression level. Caco-2 and LS174T cell lines were included as references. We characterized how SWMS conditions affected HT29-MTX-E12 cells in terms of epithelial barrier integrity, by measuring transepithelial electrical resistance, and cell metabolism, by monitoring pH and lactate production per molecule glucose of the conditioned medium. We confirmed higher MUC2 production under SWMS conditions at gene and protein level and demonstrated that this culturing method primarily stimulated cell growth. In addition, we also found evidence for a more aerobic cell metabolism under SWMS, as shown previously for similar models. In summary, we suggest different mechanisms by which MUC2 production is enhanced under SWMS and propose potential applications of this model in future studies.

OC.07.6 GELENTERUM AMELIORATES SEVERITY OF COLITIS IN DSS MURINE MODEL, WHILE MODULATING GUT MICROBIOTA AND INTESTINAL MUCUS LAYER

2013 ◽  
Vol 45 ◽  
pp. S72-S73
Author(s):  
F. Scaldaferri ◽  
L.R. Lopetuso ◽  
V. Petito ◽  
V. Gerardi ◽  
M. Bilotta ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Murine Model ◽  
Mucus Layer ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer
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