scholarly journals Immunological design of commensal communities to treat intestinal infection and inflammation

2021 ◽  
Vol 17 (1) ◽  
pp. e1009191
Author(s):  
Rebecca L. Brown ◽  
Max L. Y. Larkinson ◽  
Thomas B. Clarke
Keyword(s):  
Intracellular Signaling ◽  
Intestinal Inflammation ◽  
Secondary Response ◽  
Mucosal Barrier ◽  
Intestinal Immunity ◽  
Antibiotic Resistant ◽  
Commensal Species ◽  
Mucosal Barrier Function ◽  
Infection And Inflammation ◽  
Tlr4 Activation

The immunological impact of individual commensal species within the microbiota is poorly understood limiting the use of commensals to treat disease. Here, we systematically profile the immunological fingerprint of commensals from the major phyla in the human intestine (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria) to reveal taxonomic patterns in immune activation and use this information to rationally design commensal communities to enhance antibacterial defenses and combat intestinal inflammation. We reveal that Bacteroidetes and Firmicutes have distinct effects on intestinal immunity by differentially inducing primary and secondary response genes. Within these phyla, the immunostimulatory capacity of commensals from the Bacteroidia class (Bacteroidetes phyla) reflects their robustness of TLR4 activation and Bacteroidia communities rely solely on this receptor for their effects on intestinal immunity. By contrast, within the Clostridia class (Firmicutes phyla) it reflects the degree of TLR2 and TLR4 activation, and communities of Clostridia signal via both of these receptors to exert their effects on intestinal immunity. By analyzing the receptors, intracellular signaling components and transcription factors that are engaged by different commensal species, we identify canonical NF-κB signaling as a critical rheostat which grades the degree of immune stimulation commensals elicit. Guided by this immunological analysis, we constructed a cross-phylum consortium of commensals (Bacteroides uniformis, Bacteroides ovatus, Peptostreptococcus anaerobius and Clostridium histolyticum) which enhances innate TLR, IL6 and macrophages-dependent defenses against intestinal colonization by vancomycin resistant Enterococci, and fortifies mucosal barrier function during pathological intestinal inflammation through the same pathway. Critically, the setpoint of intestinal immunity established by this consortium is calibrated by canonical NF-κB signaling. Thus, by profiling the immunological impact of major human commensal species our work paves the way for rational microbiota reengineering to protect against antibiotic resistant infections and to treat intestinal inflammation.

scholarly journals Epithelial EP4 plays an essential role in maintaining homeostasis in colon

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoshihide Matsumoto ◽  
Yuki Nakanishi ◽  
Takuto Yoshioka ◽  
Yuichi Yamaga ◽  
Tomonori Masuda ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Secretory Cell ◽  
Intestinal Inflammation ◽  
Mucosal Barrier ◽  
Cell Lineages ◽  
Ep4 Receptor ◽  
Microbial Invasion ◽  
Inflammatory Status ◽  
Mucosal Barrier Function

Abstract Colonic epithelial cells comprise the mucosal barrier, and their dysfunction promotes microbial invasion from the gut lumen and induces the development of intestinal inflammation. The EP4 receptor is known to mediate the protective effect of prostaglandin (PG) E2 in the gastrointestinal tract; however, the exact role of epithelial EP4 in intestinal pathophysiology remains unknown. In the present study, we aimed to investigate the role of epithelial EP4 in maintaining colonic homeostasis by characterizing the intestinal epithelial cell-specific EP4 knockout (EP4 cKO) mice. Mice harboring the epithelial EP4 deletion showed significantly lower colonic crypt depth and lower numbers of secretory cell lineages, as well as impaired epithelial cells in the colon. Interestingly, EP4-deficient colon epithelia showed a higher number of apoptotic cells. Consistent with the defect in mucosal barrier function of colonic epithelia and secretory cell lineages, EP4 cKO colon stroma showed enhanced immune cell infiltration, which was accompanied by increased production of inflammatory cytokines. Furthermore, EP4-deficient colons were susceptible to dextran sulfate sodium (DSS)-induced colitis. Our study is the first to demonstrate that epithelial EP4 loss resulted in potential “inflammatory” status under physiological conditions. These findings provided insights into the crucial role of epithelial PGE2/EP4 axis in maintaining intestinal homeostasis.

Intestinal Inflammation and Mucosal Barrier Function

2014 ◽  
Vol 20 (12) ◽  
pp. 2394-2404 ◽  
Author(s):  
Fermín Sánchez de Medina ◽  
Isabel Romero-Calvo ◽  
Cristina Mascaraque ◽  
Olga Martínez-Augustin
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Mucosal Barrier ◽  
Mucosal Barrier Function

scholarly journals Alleviative Effects of Exopolysaccharide Produced by Lactobacillus helveticus KLDS1.8701 on Dextran Sulfate Sodium-Induced Colitis in Mice

2021 ◽  
Vol 9 (10) ◽  
pp. 2086
Author(s):  
Yin Liu ◽  
Shujuan Zheng ◽  
Jiale Cui ◽  
Tingting Guo ◽  
Jingtao Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Lactobacillus Helveticus ◽  
Mucosal Barrier ◽  
Microbiota Composition ◽  
Mucosal Barrier Function ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

Ulcerative colitis (UC) is a non-specific chronic inflammatory disease with lesions located in the colon and rectum. The aim of this study was to evaluate the anti-inflammatory effects of exopolysaccharide-1 (EPS-1) isolated by L. helveticus KLDS1.8701 on UC. The anti-inflammatory effects of EPS-1 were studied using dextran sulphate sodium (DSS)-induced UC model. In vivo results showed that EPS-1 administration significantly ameliorated weight loss, colon shortening, disease activity index (DAI) score, myeloperoxidase (MPO) activity, and colon tissue damage. In addition, EPS-1 administration significantly decreased the levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. Meanwhile, EPS-1 administration significantly up-regulated the expression of tight junction proteins and mucin. Furthermore, EPS-1 administration modulated gut microbiota composition caused by DSS and increased the short-chain fatty acids (SCFAs) levels. Collectively, our study showed the alleviative effects of EPS- isolated by L. helveticus KLDS1.8701 on DSS-induced UC via alleviating intestinal inflammation, improving mucosal barrier function, and modulating gut microbiota composition.

scholarly journals Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin-yu You ◽  
Han-yu Zhang ◽  
Xu Han ◽  
Fang Wang ◽  
Peng-wei Zhuang ◽  
...  
Keyword(s):  
Nervous System ◽  
Metabolic Diseases ◽  
Intestinal Inflammation ◽  
Acute Stress ◽  
Intestinal Barrier ◽  
Cerebrovascular Diseases ◽  
Mucosal Barrier ◽  
Intestinal Mucosal Barrier ◽  
Mucosal Barrier Function ◽  
Irritable Bowel

Inflammatory bowel disease, irritable bowel syndrome and severe central nervous system injury can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases. Hence, repairing the intestinal barrier represents a potential therapeutic target for many diseases. Enteral afferent nerves, efferent nerves and the intrinsic enteric nervous system (ENS) play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors. In addition, intestinal microorganisms and their metabolites play a regulatory role in the intestinal mucosal barrier. This paper primarily discusses the interactions between norepinephrine and β-adrenergic receptors, cholinergic anti-inflammatory pathways, nociceptive receptors, complex ENS networks, gut microbes and various immune cells with their secreted cytokines to summarize the key roles in regulating intestinal inflammation and improving mucosal barrier function.

scholarly journals Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengxia Wang ◽  
Biqiang Zhou ◽  
Weihong Cong ◽  
Miao Zhang ◽  
Ziwen Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathway ◽  
Intestinal Inflammation ◽  
Wnt Signaling Pathway ◽  
Indole Alkaloid ◽  
Mucosal Barrier ◽  
Hippo Signaling ◽  
Protective Effects ◽  
Evodia Rutaecarpa ◽  
Mucosal Barrier Function

Evodiamine (EVO), an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth.、Evodia rutaecarpa (Juss.) Benth. Var. bodinieri (Dode) Huang or Evodia rutaecarpa (Juss.) Benth. Var. officinalis (Dode) Huang, has anti-inflammatory and anti-tumor activities. Our previous study found that EVO attenuates colitis by regulating gut microbiota and metabolites. However, little is known about its effect on colitis-associated cancer (CAC). In this study, the protective effects of EVO on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and tumor mice were observed, and the underlying potential mechanism was clarified. The results suggested that EVO ameliorated AOM/DSS-induced colitis by inhibiting the intestinal inflammation and improving mucosal barrier function. And EVO significantly reduced the number and size of AOM/DSS-induced colorectal tumors along with promoted apoptosis and inhibited proliferation of epithelial cell. Moreover, EVO promoted the enrichment of SCFAs-producing bacteria and reduced the levels of the pro-inflammatory bacteria, which contributes to the changes of microbiota metabolism, especially tryptophan metabolism. Furthermore, inflammatory response (like Wnt signaling pathway、Hippo signaling pathway and IL-17 signaling pathway) were effectively alleviated by EVO. Our study demonstrated that the protective therapeutic action of EVO on CAC is to inhibit the development of intestinal inflammation-cancer by regulating gut microbiota metabolites and signaling pathways of colon intestinal epithelial, which may represent a novel agent for colon cancer prevention via manipulation of gut microbiota.

scholarly journals Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

2010 ◽  
Vol 299 (1) ◽  
pp. G43-G53 ◽  
Author(s):  
P. L. Beck ◽  
E. Ihara ◽  
S. A. Hirota ◽  
J. A. MacDonald ◽  
D. Meng ◽  
...  
Keyword(s):  
Immune Response ◽  
Barrier Function ◽  
Wound Repair ◽  
Intestinal Inflammation ◽  
Leukocyte Recruitment ◽  
Mucosal Barrier ◽  
Trefoil Factor ◽  
Wild Type ◽  
Trefoil Factor 3 ◽  
Mucosal Barrier Function

Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P-selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3−/− mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double-knockout mice (TFF3/Fuc-TVII−/− mice) were generated by mating TFF3−/− and Fuc-TVII−/− mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII−/−, TFF3−/−, Fuc-TVII−/−, or wild-type mice. Loss of Fuc-TVII resulted in a reduction in disease severity whereas TFF3−/− mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc-TVII in TFF3−/− mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/β-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response.

scholarly journals A Role of Exopolysaccharide Produced by Streptococcus thermophilus in the Intestinal Inflammation and Mucosal Barrier in Caco-2 Monolayer and Dextran Sulphate Sodium-Induced Experimental Murine Colitis

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 513 ◽  
Author(s):  
Yun Chen ◽  
Ming Zhang ◽  
Fazheng Ren
Keyword(s):  
Tight Junction ◽  
Intestinal Inflammation ◽  
Gastrointestinal Disease ◽  
Streptococcus Thermophilus ◽  
Water Soluble ◽  
Mucosal Barrier ◽  
Dextran Sulphate ◽  
Dextran Sulphate Sodium ◽  
Junction Protein ◽  
Mucosal Barrier Function

Exopolysaccharide (EPS) produced by probiotics may play an important role in gastrointestinal disease prevention, including ulcerative colitis. However, there is no literature reporting on the intervention effects of purified EPS. The aim of this study was to investigate the alleviating effect of the purified EPS produced by Streptococcus thermophilus MN-BM-A01 on murine model of colitis induced by dextran sulphate sodium (DSS). A water-soluble heteropolysaccharide (EPS-1) isolated from MN-BM-A01 was composed of rhamnose, glucose, galactose, and mannose in a molar ratio of 12.9:26.0:60.9:0.25, with molecular weight of 4.23 × 105 Da. After EPS-1 administration, the disease severity of mouse colitis was significantly alleviated, mainly manifesting as the decrease of disease activity index and mitigated colonic epithelial cell injury. Meanwhile, pro-inflammatory cytokines levels (tumor necrosis factor-α, interleukin-6, and interferon-γ) were significantly suppressed, the reduced expressions of tight junction protein (claudin-1, occludin, and E-canherin) were counteracted. In addition, the results in vitro showed that EPS-1 protected intestinal barrier integrity from the disruption by lipopolysaccharide in Caco-2 monolayer, increased expression of tight junction and alleviated pro-inflammatory response. Collectively, our study confirmed the protective effects of purified EPS produced by Streptococcus thermophilus on acute colitis via alleviating intestinal inflammation and improving mucosal barrier function.

scholarly journals Antibiotic Treatment Alters the Colonic Mucus Layer and Predisposes the Host to ExacerbatedCitrobacter rodentium-Induced Colitis

2011 ◽  
Vol 79 (4) ◽  
pp. 1536-1545 ◽  
Author(s):  
M. Wlodarska ◽  
B. Willing ◽  
K. M. Keeney ◽  
A. Menendez ◽  
K. S. Bergstrom ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Mucosal Barrier ◽  
Intestinal Immunity ◽  
Mucus Layer ◽  
Microbial Composition ◽  
Bacterial Stimulation ◽  
Increased Susceptibility ◽  
Stimulation Of

ABSTRACTAntibiotics are often used in the clinic to treat bacterial infections, but the effects of these drugs on microbiota composition and on intestinal immunity are poorly understood.Citrobacter rodentiumwas used as a model enteric pathogen to investigate the effect of microbial perturbation on intestinal barriers and susceptibility to colitis. Streptomycin and metronidazole were used to induce alterations in the composition of the microbiota prior to infection withC. rodentium. Metronidazole pretreatment increased susceptibility toC. rodentium-induced colitis over that of untreated and streptomycin-pretreated mice, 6 days postinfection. Both antibiotic treatments altered microbial composition, without affecting total numbers, but metronidazole treatment resulted in a more dramatic change, including a reduced population ofPorphyromonadaceaeand increased numbers of lactobacilli. Disruption of the microbiota with metronidazole, but not streptomycin treatment, resulted in an increased inflammatory tone of the intestine characterized by increased bacterial stimulation of the epithelium, altered goblet cell function, and thinning of the inner mucus layer, suggesting a weakened mucosal barrier. This reduction in mucus thickness correlates with increased attachment ofC. rodentiumto the intestinal epithelium, contributing to the exacerbated severity ofC. rodentium-induced colitis in metronidazole-pretreated mice. These results suggest that antibiotic perturbation of the microbiota can disrupt intestinal homeostasis and the integrity of intestinal defenses, which protect against invading pathogens and intestinal inflammation.

Gut microbiota mediates the effects of inulin on enhancing sulfomucin production and mucosal barrier function in a pig model

2021 ◽  
Author(s):  
Bing Xia ◽  
weida wu ◽  
Li Zhang ◽  
Xiaobin Wen ◽  
Jingjing Xie ◽  
...  
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Community Composition ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Microbial Community Composition ◽  
Mucosal Barrier ◽  
Dietary Fibers ◽  
Beneficial Effects ◽  
Mucosal Barrier Function

Dietary fibers (DFs) have many beneficial effects on intestinal health by ameliorating intestinal inflammation and modulating the microbial community composition, thereby affecting the barrier function. This study aims to characterize...

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