scholarly journals A52 BUTYRATE SUPPLEMENTATION AMELIORATES DAMAGE CAUSED BY ENTERIC CITROBACTER RODENTIUM INFECTION

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 61-62
Author(s):  
L S Celiberto ◽  
G Healey ◽  
J Xu ◽  
L Xia ◽  
B Vallance
Keyword(s):  
Butyric Acid ◽  
Tissue Damage ◽  
Intestinal Inflammation ◽  
Bacterial Colonization ◽  
Clinical Signs ◽  
Host Susceptibility ◽  
Mucus Layer ◽  
Citrobacter Rodentium ◽  
Oral Gavage ◽  
Intestinal Mucus

Abstract Background Patients with inflammatory bowel disease (IBD) often display a dysbiotic microbiome as well as a defective intestinal mucus layer, which appears thinner and more penetrable than the mucus layer of healthy subjects. Tributyrin (TB), a prodrug of butyric acid, has shown beneficial effects in models of IBD due to its anti-inflammatory effects. We previously showed that mice lacking the major intestinal mucin Muc2 (Muc2-/-) or lacking the “Core1” enzyme responsible for glycosylating Muc2 (C1galt1-/-) were highly susceptible to infection by Citrobacter rodentium, a murine model of intestinal inflammation. Aims The study explored the role of gut mucus in providing host defense against C. rodentium, as well as the effects of TB supplementation in the prevention of mucosal damage in this model. Methods Six to ten week old wildtype (WT), Muc2-/-, flox control (C1galt1f/f) and C1galt1-/- mice were infected with C. rodentium (∼2.5 × 108 CFU) by oral gavage. For TB supplementation experiments, mice received 100µL of TB or glycerol as a control by oral gavage every other day starting on day 1 post infection. Mice were monitored daily throughout the experiment and were euthanized at day 6 of infection. Several tissues of interest were collected to verify bacterial colonization in the gut and at systemic sites as well as histological tissue damage. Cecal contents were collected for the analysis of short chain fatty acids, while blood was collected by cardiac puncture after oral gavage with FITC-dextran to measure intestinal permeability. Results While WT and C1galt1f/f mice were only modestly susceptible to C. rodentium infection, Muc2-/- and C1galt1-/- mice displayed dramatically (100 fold) increased pathogen burdens, significantly greater intestinal macroscopic and histopathology scores, and heightened barrier disruption as compared to controls. Moreover, Muc2-/- and C1galt1-/- mice showed significantly lower levels of butyric acid as compared to control mice under baseline conditions. Interestingly, when supplemented with TB, Muc2-/- and C1galt1-/- proved less susceptible to C. rodentium infection, as indicated by reduced weight loss and clinical signs of colitis, while pathogen burdens were greatly reduced as was histological tissue damage, and epithelial barrier dysfunction. The same protection was conferred when TB was administered as a dietary supplementation, thus confirming its beneficial effect in protecting mice against C. rodentium infection. Conclusions These findings demonstrate that intestinal mucus controls host susceptibility to C. rodentium infection via control over butyrate levels, and highlight the need to explore the mechanisms by which gut mucus modulates the resident microbiota and its metabolites. Funding Agencies CCC, CIHR

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 Host Susceptibility to the Attaching and Effacing Bacterial Pathogen Citrobacter rodentium

2003 ◽  
Vol 71 (6) ◽  
pp. 3443-3453 ◽  
Author(s):  
Bruce A. Vallance ◽  
Wanyin Deng ◽  
Kevan Jacobson ◽  
B. Brett Finlay
Keyword(s):  
Bacterial Translocation ◽  
Cell Apoptosis ◽  
Bacterial Colonization ◽  
Bacterial Load ◽  
Crypt Cell ◽  
Host Susceptibility ◽  
Mouse Strains ◽  
Citrobacter Rodentium ◽  
Mesenteric Lymph Nodes ◽  
Susceptible Mouse

ABSTRACT Many studies have shown that genetic susceptibility plays a key role in determining whether bacterial pathogens successfully infect and cause disease in potential hosts. Surprisingly, whether host genetics influence the pathogenesis of attaching and effacing (A/E) bacteria such as enteropathogenic and enterohemorrhagic Escherichia coli has not been examined. To address this issue, we infected various mouse strains with Citrobacter rodentium, a member of the A/E pathogen family. Of the strains tested, the lipopolysaccharide (LPS) nonresponder C3H/HeJ mouse strain experienced more rapid and extensive bacterial colonization than did other strains. Moreover, the high bacterial load in these mice was associated with accelerated crypt hyperplasia, mucosal ulceration, and bleeding, together with very high mortality rates. Interestingly, the basis for the increased susceptibility was not due to LPS hyporesponsiveness, as the genetically related but LPS-responsive C3H/HeOuJ and C3H/HeN mouse strains were also susceptible to infection. Analysis of the intestinal pathology in these susceptible strains revealed significant crypt epithelial cell apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end label staining) as well as bacterial translocation to the mesenteric lymph nodes. Further studies with infection of SCID (T- and B-lymphocyte-deficient) C3H/HeJ mice demonstrated that loss of lymphocytes had no effect on bacterial numbers but did reduce crypt cell apoptosis and delayed mortality. These studies thus identify the adaptive immune system, crypt cell apoptosis, and bacterial translocation but not LPS responsiveness as contributing to the tissue pathology and mortality seen during C. rodentium infection of highly susceptible mouse strains. Determining the basis for these strains' susceptibility to intestinal colonization by an A/E pathogen will be the focus of future studies.

scholarly journals Protective and Anti-Inflammatory Effects of Protegrin-1 on Citrobacter rodentium Intestinal Infection in Mice

2021 ◽  
Vol 22 (17) ◽  
pp. 9494
Author(s):  
Celina Osakowicz ◽  
Lauren Fletcher ◽  
Jeff L. Caswell ◽  
Julang Li
Keyword(s):  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Intestinal Inflammation ◽  
Clinical Signs ◽  
Significant Rise ◽  
Resistant Bacteria ◽  
Protective Effects ◽  
Citrobacter Rodentium ◽  
Intestinal Infection ◽  
Infectious Colitis

Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced Citrobacter rodentium intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis.

scholarly journals Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2612-2619 ◽  
Author(s):  
Lisa K. Nelson ◽  
Genevieve H. D'Amours ◽  
Kimberley M. Sproule-Willoughby ◽  
Douglas W. Morck ◽  
Howard Ceri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Tissue Damage ◽  
Inflammatory Markers ◽  
Bacterial Colonization ◽  
Opportunistic Pathogen ◽  
Infection Model ◽  
Chronic Infections ◽  
Strain Pao1 ◽  
Rat Prostate

Pseudomonas aeruginosa frequently acts as an opportunistic pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.

A simulated mucus layer protects Lactobacillus reuteri from the inhibitory effects of linoleic acid

2013 ◽  
Vol 4 (4) ◽  
pp. 299-312 ◽  
Author(s):  
R. De Weirdt ◽  
E. Coenen ◽  
B. Vlaeminck ◽  
V. Fievez ◽  
P. Van den Abbeele ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Lactobacillus Reuteri ◽  
Close Contact ◽  
Mucus Layer ◽  
Inhibitory Effects ◽  
Intestinal Mucus ◽  
Gut Microbe ◽  
Protective Environment ◽  
Bacterial Cell Membrane ◽  
High Concentrations

Lactobacillus reuteri is a commensal, beneficial gut microbe that colonises the intestinal mucus layer, where it makes close contact with the human host and may significantly affect human health. Here, we investigated the capacity of linoleic acid (LA), the most common polyunsaturated fatty acid (PUFA) in a Western-style diet, to affect L. reuteri ATCC PTA 6475 prevalence and survival in a simulated mucus layer. Short-term (1 h) survival and mucin-agar adhesion assays of a log-phase L. reuteri suspension in intestinal water demonstrated that the simulated mucus layer protected L. reuteri against the inhibitory effects of LA by lowering its contact with the bacterial cell membrane. The protective effect of the simulated mucus layer was further evaluated using a more complex and dynamic model of the colon microbiota (SHIME®), in which L. reuteri survival was monitored during 6 days of daily exposure to LA in the absence (L-SHIME) and presence (M-SHIME) of a simulated mucus layer. After 6 days, luminal L- and M-SHIME L. reuteri plate counts had decreased by 3.1±0.5 and 2.6±0.9 log cfu/ml, respectively. Upon supplementation of 1.0 g/l LA, the decline in the luminal L. reuteri population started earlier than was observed for the control. In contrast, mucin-agar levels of L. reuteri (in the M-SHIME) remained unaffected throughout the experiment even in the presence of high concentrations of LA. Overall, the results of this study indicate the importance of the mucus layer as a protective environment for beneficial gut microbes to escape from stress by high loads of the antimicrobial PUFA LA to the colon, i.e. due to a Western-style diet.

scholarly journals Revisiting Ophidiomycosis (Snake Fungal Disease) After a Decade of Targeted Research

2021 ◽  
Vol 8 ◽  
Author(s):  
Christina M. Davy ◽  
Leonard Shirose ◽  
Doug Campbell ◽  
Rachel Dillon ◽  
Christina McKenzie ◽  
...  
Keyword(s):  
Large Scale ◽  
Sublethal Effects ◽  
Clinical Signs ◽  
Fungal Disease ◽  
Host Susceptibility ◽  
Current Evidence ◽  
Molecular Testing ◽  
Population Declines ◽  
Snake Fungal Disease ◽  
Free Ranging

Emerging infectious diseases (EIDs) are typically characterized by novelty (recent detection) and by increasing incidence, distribution, and/or pathogenicity. Ophidiomycosis, also called snake fungal disease, is caused by the fungus Ophidiomyces ophidiicola (formerly “ophiodiicola”). Ophidiomycosis has been characterized as an EID and as a potential threat to populations of Nearctic snakes, sparking over a decade of targeted research. However, the severity of this threat is unclear. We reviewed the available literature to quantify incidence and effects of ophidiomycosis in Nearctic snakes, and to evaluate whether the evidence supports the ongoing characterization of ophidiomycosis as an EID. Data from Canada remain scarce, so we supplemented the literature review with surveys for O. ophidiicola in the Canadian Great Lakes region. Peer-reviewed reports of clinical signs consistent with ophidiomycosis in free-ranging, Nearctic snakes date back to at least 1998, and retrospective molecular testing of samples extend the earliest confirmed record to 1986. Diagnostic criteria varied among publications (n = 33), confounding quantitative comparisons. Ophidiomycosis was diagnosed or suspected in 36/121 captive snakes and was fatal in over half of cases (66.7%). This result may implicate captivity-related stress as a risk factor for mortality from ophidiomycosis, but could also reflect reporting bias (i.e., infections are more likely to be detected in captive snakes, and severe cases are more likely to be reported). In contrast, ophidiomycosis was diagnosed or suspected in 441/2,384 free-ranging snakes, with mortality observed in 43 (9.8 %). Ophidiomycosis was only speculatively linked to population declines, and we found no evidence that the prevalence of the pathogen or disease increased over the past decade of targeted research. Supplemental surveys and molecular (qPCR) testing in Ontario, Canada detected O. ophidiicola on 76 of 657 free-ranging snakes sampled across ~136,000 km2. The pathogen was detected at most sites despite limited and haphazard sampling. No large-scale mortality was observed. Current evidence supports previous suggestions that the pathogen is a widespread, previously unrecognized endemic, rather than a novel pathogen. Ophidiomycosis may not pose an imminent threat to Nearctic snakes, but further research should investigate potential sublethal effects of ophidiomycosis such as altered reproductive success that could impact population growth, and explore whether shifting environmental conditions may alter host susceptibility.

scholarly journals Hyaluronan-induced alterations of the gut microbiome protects mice against Citrobacter rodentium infection and intestinal inflammation

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Tangyou Mao ◽  
Chien-Wen Su ◽  
Qiaorong Ji ◽  
Chih-Yu Chen ◽  
Rongjun Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Citrobacter Rodentium

scholarly journals Denture Stomatitis: Report of a Case with Rarely Used Treatment Modality and Review of Literature

2020 ◽  
Vol 4 (5) ◽  
pp. 116-119
Author(s):  
Parul Uppal Malhotra ◽  
Neera Ohri ◽  
Yagyeshwar Malhotra ◽  
Anindita Mallik
Keyword(s):  
Candida Albicans ◽  
Candida Species ◽  
Fungal Infections ◽  
Bacterial Colonization ◽  
Oral Candidiasis ◽  
Clinical Signs ◽  
Fungal Growth ◽  
Dimorphic Fungus ◽  
Denture Stomatitis ◽  
Microbial Invasion

Candida albicans is the most common Candida species isolated from the oral cavity both in healthy and diseased. Candida albicans is a dimorphic fungus existing both in blastopore phase (yeast phase) and the hyphal or mycelial phase. Although these organisms typically colonize mucocutaneous surfaces, the latter can be portals of entry into deeper tissues when host defences are compromised. Denture stomatitis is a common form of oral candidiasis that manifests as a diffuse inflammation of the maxillary denture bearing areas & is associated with angular cheilitis. At least 70% of individuals with clinical signs of denture stomatitis exhibit fungal growth & these conditions most likely result from yeast colonization of the oral mucosa combined with Bacterial colonization. Candida species act as an endogenous infecting agent on tissue predisposed by chronic trauma to microbial invasion. At one time, oral fungal infections were rare findings in general dentist's office. They were more commonly seen in hospitalized and severely debilitated patients. However with enhanced medical and pharmaceutical technology, increasing numbers of ambulatory immunosuppressed individuals with oral fungal infections are seeking out general dentists for diagnosis and treatment of these lesions.

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