A Spore‐Forming Probiotic Supplement Improves the Intestinal Immune Response and Protects the Intestinal Health During Recurrent Clostridioides difficile Colonization in Mice

2020 ◽  
Vol 44 (8) ◽  
pp. 1428-1438
Author(s):  
Fatemeh Ramezani Kapourchali ◽  
Bryan Glueck ◽  
Yingchun Han ◽  
David Shapiro ◽  
Clifton G. Fulmer ◽  
...  
Keyword(s):  
Immune Response ◽  
Intestinal Health ◽  
Clostridioides Difficile

scholarly journals Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Criado-Mesas ◽  
N. Abdelli ◽  
A. Noce ◽  
M. Farré ◽  
J. F. Pérez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Barrier Function ◽  
Nutrient Transport ◽  
Gene Expression Pattern ◽  
Vaccine Dose ◽  
Special Focus ◽  
Intestinal Health ◽  
Barrier Failure ◽  
Expression Of Genes

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.

scholarly journals Ursodeoxycholic Acid (UDCA) Mitigates the Host Inflammatory Response during Clostridioides difficile Infection by Altering Gut Bile Acids

2020 ◽  
Vol 88 (6) ◽  
Author(s):  
Jenessa A. Winston ◽  
Alissa J. Rivera ◽  
Jingwei Cai ◽  
Rajani Thanissery ◽  
Stephanie A. Montgomery ◽  
...  
Keyword(s):  
Immune Response ◽  
Bile Acid ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Colonization Resistance ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile infection (CDI) is associated with increasing morbidity and mortality posing an urgent threat to public health. Recurrence of CDI after successful treatment with antibiotics is high, thus necessitating discovery of novel therapeutics against this enteric pathogen. Administration of the secondary bile acid ursodeoxycholic acid (UDCA; ursodiol) inhibits the life cycles of various strains of C. difficile in vitro, suggesting that the FDA-approved formulation of UDCA, known as ursodiol, may be able to restore colonization resistance against C. difficile in vivo. However, the mechanism(s) by which ursodiol is able to restore colonization resistance against C. difficile remains unknown. Here, we confirmed that ursodiol inhibits C. difficile R20291 spore germination and outgrowth, growth, and toxin activity in a dose-dependent manner in vitro. In a murine model of CDI, exogenous administration of ursodiol resulted in significant alterations in the bile acid metabolome with little to no changes in gut microbial community structure. Ursodiol pretreatment resulted in attenuation of CDI pathogenesis early in the course of disease, which coincided with alterations in the cecal and colonic inflammatory transcriptome, bile acid-activated receptors nuclear farnesoid X receptor (FXR) and transmembrane G-protein-coupled membrane receptor 5 (TGR5), which are able to modulate the innate immune response through signaling pathways such as NF-κB. Although ursodiol pretreatment did not result in a consistent decrease in the C. difficile life cycle in vivo, it was able to attenuate an overly robust inflammatory response that is detrimental to the host during CDI. Ursodiol remains a viable nonantibiotic treatment and/or prevention strategy against CDI. Likewise, modulation of the host innate immune response via bile acid-activated receptors FXR and TGR5 represents a new potential treatment strategy for patients with CDI.

Effects of fish origin probiotics on growth performance, immune response and intestinal health of shrimp ( Litopenaeus vannamei ) fed diets with fish meal partially replaced by soybean meal

2020 ◽  
Vol 26 (4) ◽  
pp. 1255-1265 ◽  
Author(s):  
Jiao‐Jin Zhang ◽  
Hong‐Ling Yang ◽  
Yang‐Yang Yan ◽  
Chun‐Xiao Zhang ◽  
Ji‐dan Ye ◽  
...  
Keyword(s):  
Immune Response ◽  
Growth Performance ◽  
Soybean Meal ◽  
Litopenaeus Vannamei ◽  
Fish Meal ◽  
Intestinal Health

Tilapia piscidin 4 (TP4) enhances immune response, antioxidant activity, intestinal health and protection against Streptococcus iniae infection in Nile tilapia

Aquaculture ◽  
2019 ◽  
Vol 513 ◽  
pp. 734451 ◽  
Author(s):  
Eman Zahran ◽  
Engy Risha ◽  
Samia Elbahnaswy ◽  
Hebatallah Ahmed Mahgoub ◽  
Amany Abd El-Moaty
Keyword(s):  
Immune Response ◽  
Antioxidant Activity ◽  
Nile Tilapia ◽  
Streptococcus Iniae ◽  
Intestinal Health

scholarly journals ZupT Facilitates Clostridioides difficile Resistance to Host-Mediated Nutritional Immunity

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Joseph P. Zackular ◽  
Reece J. Knippel ◽  
Christopher A. Lopez ◽  
William N. Beavers ◽  
C. Noel Maxwell ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Potential ◽  
Neutrophil Infiltration ◽  
Toxin Production ◽  
Host Protein ◽  
Content Type ◽  
Nutritional Immunity ◽  
Clostridioides Difficile ◽  
Therapeutic Development ◽  
Dependent Growth

ABSTRACT Clostridioides difficile is a spore-forming bacterium that causes severe colitis and is a major public health threat. During infection, C. difficile toxin production results in damage to the epithelium and a hyperinflammatory response. The immune response to CDI leads to robust neutrophil infiltration at the sight of infection and the deployment of numerous antimicrobials. One of the most abundant host immune factors associated with CDI is calprotectin, a metal-chelating protein with potent antimicrobial activity. Calprotectin is essential to the innate immune response to C. difficile and increasing levels of calprotectin correlate with disease severity in both adults and children with CDI. The fact that C. difficile persists in the presence of high levels of calprotectin suggests that this organism may deploy strategies to compete with this potent antimicrobial factor for essential nutrient metals during infection. In this report, we demonstrate that a putative zinc (Zn) transporter, ZupT, is employed by C. difficile to survive calprotectin-mediated metal limitation. ZupT is highly expressed in the presence of calprotectin and is required to protect C. difficile against calprotectin-dependent growth inhibition. When competing against wild-type C. difficile, zupT mutants show a defect in colonization and persistence in a murine model of infection. Together these data demonstrate that C. difficile utilizes a metal import system to combat nutritional immunity during CDI and suggest that strategies targeting nutrient acquisition in C. difficile may have therapeutic potential. IMPORTANCE During infection, pathogenic organisms must acquire essential transition metals from the host environment. Through the process of nutritional immunity, the host employs numerous strategies to restrict these key nutrients from invading pathogens. In this study, we describe a mechanism by which the important human pathogen Clostridioides difficile resists transition-metal limitation by the host. We report that C. difficile utilizes a zinc transporter, ZupT, to compete with the host protein calprotectin for nutrient zinc. Inactivation of this transporter in C. difficile renders this important pathogen sensitive to host-mediated metal restriction and confers a fitness disadvantage during infection. Our study demonstrates that targeting nutrient metal transport proteins in C. difficile is a potential avenue for therapeutic development.

scholarly journals Characterization of the Immune Response during Infection Caused by Clostridioides difficile

2019 ◽  
Vol 7 (10) ◽  
pp. 435 ◽  
Author(s):  
Hamo ◽  
Azrad ◽  
Nitzan ◽  
Peretz
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Interferon Α ◽  
T Helper 1 ◽  
Serum Samples ◽  
Mild Disease ◽  
Clostridioides Difficile ◽  
Cytokines And Chemokines ◽  
Clostridioides Difficile Infection ◽  
Macrophage Colony

The high risk of complications and death following Clostridioides difficile infection (CDI) requires identifying patients with severe disease and treating them accordingly. We characterized the immune response of CDI patients in relation to infection severity. Concentrations of 28 cytokines and chemokines were measured in serum samples, obtained from 54 CDI patients within a median timeframe of 24–48 h after laboratory confirmation of C. difficile infection. Demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined by “Score indices for Clostridioides difficile infection severity”. Of 54 patients (mean age, 76.6 years, 61.1% female), 38 (70.4%) had mild disease and 16 (29.6%) had moderate disease. Seven cytokines were associated with a more severe CDI: granulocyte-macrophage colony-stimulating factor (p = 0.0106), interleukin (IL)-1β (p = 0.004), IL-8 (p = 0.0098), IL-12p70 (p = 0.0118), interferon-α (p = 0.0282), IL-15 (p = 0.0015), and IL-2 (p = 0.0031). Additionally, there was an increased T-helper 1 response in more severe cases of CDI. Cytokines may serve as biomarkers for early prediction of CDI severity. Better and earlier assessment of illness severity will contribute to the adjustment of medical treatment, including monitoring and follow-up.

scholarly journals 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S828-S828
Author(s):  
Travis J Carlson ◽  
Bradley T Endres ◽  
Julie Le Pham ◽  
Anne J Gonzales-Luna ◽  
Faris S Alnezary ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Outcomes ◽  
Eosinophil Count ◽  
Toxin Production ◽  
Albumin Level ◽  
Binary Toxin ◽  
Inpatient Mortality ◽  
Healthcare Facilities ◽  
Clostridioides Difficile

Abstract Background The ability of Clostridioides difficile to cause clinical disease in humans is dependent on toxin production. Significantly fewer eosinophils are seen in the peripheral blood of mice infected with a binary toxin positive (CDT+) C. difficile strain. Furthermore, the presence of CDT and eosinopenia have separately been associated with increased mortality in humans with C. difficile infection (CDI). We hypothesized that CDI due to a CDT+ C. difficile strain accompanied by peripheral eosinopenia would be associated with higher odds of inpatient mortality. Methods This multicenter, retrospective cohort study included all patients ≥ 18 years of age with toxigenic CDI in which specimen ribotype data were available as part of our ongoing surveillance study. The cohort was stratified by eosinophil count (0.0 cells/μL vs. > 0.0 cells/μL). The primary outcome was inpatient mortality. A logistic regression model was developed modeling inpatient mortality as a function of the available patient covariates. All P-values were from 2-sided tests, and results were deemed statistically significant at P < 0.05. Results A total of 688 patients from 13 institutions in six cities were included. Of those, 132 had a baseline eosinophil count of 0.0 cells/µL and 556 had a baseline eosinophil count > 0.0 cells/µL. While the odds of inpatient mortality were higher among patients with eosinopenia and those infected with a CDT+ ribotype, the combination of these variables remained an independent predictor of inpatient mortality after adjusting for CCI score, WBC count, and serum albumin level (OR, 7.84; 95% CI, 1.85–33.20; P = 0.005). Conclusion This is the first attempt to study the in vivo relationship between CDT presence, human immune response, and CDI clinical outcome. We identified an association between CDT presence with concomitant eosinopenia and worsened CDI outcomes. Healthcare facilities should consider identifying this important subset of patients at the time of CDI diagnosis. Future CDI drug development might benefit from targeting C. difficile properties that impair host immune response, which may in turn decrease adverse clinical outcomes associated with this disease. Disclosures All authors: No reported disclosures.

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