Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Bushman FD
PROVIDER: S-EPMC9332131 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Purpose:Fecal microbiota transplantation (FMT) is an effective treatment option for patients with recurrent Clostridioides difficile infection (rCDI). However, there is a paucity of evidence regarding its efficacy and safety in patients with rCDI and concurrent inflammatory bowel disease (IBD). Here, we present a single-center experience of FMT for treatment of rCDI in Iranian patients with IBD. Patients and Methods:Eight patients with established IBD (7 with ulcerative colitis and 1 with Crohn's disease) who underwent at least one FMT via colonoscopy for treatment of rCDI were enrolled in this study. Demographics, pre-FMT and post-FMT IBD activity, efficacy for rCDI and adverse events (AEs) were assessed during a 6-month follow-up period. All patients had experienced 3 episodes of rCDI and were refractory to conventional therapies with metronidazole and vancomycin. Primary cure and secondary cure rates were assessed after FMT treatments. Results:A total of 10 FMTs were performed via colonoscopy in 8 patients (6/8; 75% men) with a median age of 35 years (range: 22-60). Two patients received a second FMT. Overall, the primary and secondary cure rates were 75% and 100%, respectively. Two patients developed CPE-producing C. perfringens diagnoses after second FMTs. There were no other AEs, and no patient experienced IBD flare. Conclusion:We demonstrated that FMT appears to be an effective, safe and rational therapeutic alternative for resolution of rCDI in patients with underlying IBD. Furthermore, we suggest implementing the CPE-producing C. perfringens testing in the screening of FMT donors.
| S-EPMC7509309 | biostudies-literature
Project description:Clostridioides (Clostridium) difficile is the major cause of healthcare antibiotic-associated diarrhoea. However, extra-intestinal manifestations of Clostridioides (Clostridium) difficile infection (CDI) (including bacteremia and tissue infection) are extremely rare. We report a case of extraintestinal CDI after surgery. The isolate of C. difficile was not the PCR ribotype 027. However, this isolate produced toxins A and B. The patient underwent a follow-up examination 30 days after discharge, which showed complete recovery. This case report adds to existing knowledge of CDI.
| S-EPMC7475194 | biostudies-literature
Project description:OBJECTIVES:Cholecystectomy (CCY) is associated with increased faecal levels of secondary bile acids. Secondary bile acids confer resistance to Clostridioides difficile infection (CDI, formerly Clostridium difficile infection) in animal studies. This study tested the hypothesis that CCY confers protection against CDI by increasing gut levels of secondary bile acids. METHODS:This was a retrospective case-control study. Adults hospitalized between January 2010 and June 2017 at our institution were included. CDI cases were defined as a positive stool PCR followed by anti-CDI treatment and were matched 1:1:1 with two control groups (those who tested negative for CDI and those who were not tested for CDI) by sex, age group, body mass index (BMI), and exposure to antibiotics. CCY was defined as a history of CCY at least 6 months prior to the index C. difficile test or the index admission date in the untested controls. Conditional logistic regression modelling was used to estimate the relationship between remote CCY and risk for CDI. RESULTS:The final study population was 7077 (2359 CDI cases, 2359 matched controls without CDI, and 2359 matched controls not tested for CDI). Rates of remote CCY did not differ among the three groups (14.4% vs. 15.5% vs. 14.2%) and this result was unchanged after adjusting for additional clinical factors (adjusted OR 0.90, 95% CI 0.76-1.06 comparing CDI cases vs. matched controls without CDI; adjusted OR 1.04, 95% CI 0.78-1.39 comparing CDI cases vs. matched controls not tested for CDI). CONCLUSIONS:There was no association between remote CCY and risk for CDI.
| S-EPMC6589130 | biostudies-literature
Project description:Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea and places a significant burden on patients and the health care system. Statins could lead to improvements in CDI clinical response due their pleiotropic effects, including immunomodulatory and lipid-lowering effects; however, few studies have assessed this association. The primary objective of this study was to compare CDI health outcomes in statin users and non-users in a national cohort of patients. This was a retrospective cohort study of all adult CDI patients receiving care from the Veterans Health Administration from 2002 to 2014. Patients were divided into two groups based on statin exposure 90 days prior to and during their first CDI encounter. CDI health outcomes, including mortality and CDI recurrence, were compared using a propensity-score matched cohort of statin users and non-users and multivariable logistic regression. A total of 26,149 patients met study inclusion criteria, of which 173 statins-users and 173 non-users were propensity score matched. Thirty-day mortality was significantly lower among statins users with CDI (12.7%) compared to non-users (20.2%) (aOR 0.34; 95% CI 0.16-0.72). Sixty-day CDI recurrence was non-significantly lower among statin-users (9.0%) compared to non-users (16.6%) (aOR 0.68; 95% CI 0.29-1.59). In this nationally-representative study of veterans with CDI, statin use was associated with lower 30-day mortality compared to non-use. Statin use was not associated with 60-day CDI recurrence.
| S-EPMC6538245 | biostudies-other
Project description:BackgroundPersonalized medicine requires finding relationships between variables that influence a patient's phenotype and predicting an outcome. Sparse generalized canonical correlation analysis identifies relationships between different groups of variables. This method requires establishing a model of the expected interaction between those variables. Describing these interactions is challenging when the relationship is unknown or when there is no pre-established hypothesis. Thus, our aim was to develop a method to find the relationships between microbiome and host transcriptome data and the relevant clinical variables in a complex disease, such as Crohn's disease.ResultsWe present here a method to identify interactions based on canonical correlation analysis. We show that the model is the most important factor to identify relationships between blocks using a dataset of Crohn's disease patients with longitudinal sampling. First the analysis was tested in two previously published datasets: a glioma and a Crohn's disease and ulcerative colitis dataset where we describe how to select the optimum parameters. Using such parameters, we analyzed our Crohn's disease data set. We selected the model with the highest inner average variance explained to identify relationships between transcriptome, gut microbiome and clinically relevant variables. Adding the clinically relevant variables improved the average variance explained by the model compared to multiple co-inertia analysis.ConclusionsThe methodology described herein provides a general framework for identifying interactions between sets of omic data and clinically relevant variables. Following this method, we found genes and microorganisms that were related to each other independently of the model, while others were specific to the model used. Thus, model selection proved crucial to finding the existing relationships in multi-omics datasets.
| S-EPMC7870068 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation that includes Crohn´s disease (CD) and ulcerative colitis (UC). Although the etiology is still unknown, some specific factors have been directly related to IBD, including genetic factors, abnormal intestinal immunity, and/or gut microbiota modifications. Recent findings highlight the primary role of the gut microbiota closely associated with a persistent inappropriate inflammatory response. This gut environment of dysbiosis in a susceptible IBD host can increasingly worsen and lead to colonization and infection with some opportunistic pathogens, especially Clostridium difficile. C. difficile is an intestinal pathogen considered the main cause of antibiotic-associated diarrhea and colitis and an important complication of IBD, which can trigger or worsen an IBD flare. Recent findings have highlighted the loss of bacterial cooperation in the gut ecosystem, as well as the pronounced intestinal dysbiosis, in patients suffering from IBD and concomitant C. difficile infection (CDI). The results of intestinal microbiota studies are still limited and often difficult to compare because of the variety of disease conditions. However, these data provide important clues regarding the main modifications and interrelations in the complicated gut ecosystem to better understand both diseases and to take advantage of the development of new therapeutic strategies. In this review, we analyze in depth the gut microbiota changes associated with both forms of IBD and CDI and their similarity with the dysbiosis that occurs in CDI. We also discuss the metabolic pathways that favor the proliferation or decrease in several important taxa directly related to the disease.
| S-EPMC7524151 | biostudies-literature
Project description:IntroductionClostridioides difficile infection (CDI) rates and outcomes can vary based on differences in testing strategy. Our aim was to assess the prevalence of toxin detection in inflammatory bowel disease (IBD) when compared to those without IBD. Secondly, the clinical outcomes of CDI in IBD were assessed using two-step testing strategies.MethodsWe included patients undergoing CDI testing from four academic centers in the United States between January 1, 2018 and June 30, 2020. First the prevalence of toxin detection was compared between individuals with IBD and those without IBD. Secondly, among patients with IBD a primary composite outcome of abdominal colectomy, admission to an intensive care unit (ICU) or death within 30 days of C. difficile testing was assessed across the three categorical groups (screen positive/toxin positive, screen positive/toxin negative and screen negative assay) resulting from the two-step testing strategy.ResultsWhen comparing individuals with a positive screening assay, patients with IBD were less likely to have toxin detected by enzyme immunoassay (EIA) as compared to the non-IBD population (22/145 (15.2%) vs. 413/1144 (36.1%), p < 0.0001). Among all patients with IBD (n = 300), twenty-five (8.3%) had a screen positive assay/toxin positive assay, 136 (45.3%) had a screen positive/toxin negative assay and 139 (46.3%) had a negative screening assay. No significant difference in the primary composite outcome was detected across the three groups (p = 0.566).ConclusionWhen compared to those without IBD, patients with IBD have a reduced proportion of cases of C. difficile with toxin positivity. Differences in clinical outcomes among patients with IBD were not detected and limited by the infrequent detection of expressed toxin.
| S-EPMC9426007 | biostudies-literature
Project description:AimTo address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare.MethodsA systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations.ResultsIn those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not.ConclusionStrong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.
| S-EPMC5526769 | biostudies-literature
Project description:BackgroundClostridioides difficile infection (CDI) is an infectious nosocomial disease caused by Clostridioides difficile, an opportunistic pathogen that occurs in the intestine after extensive antibiotic regimens.ResultsNine C. difficile strains (CBA7201-CBA7209) were isolated from nine patients diagnosed with CDI at the national university hospital in Korea, and the whole genomes of these strains were sequenced to identify their genomic characteristics. Comparative genomic analysis was performed using 51 reference strains and the nine isolated herein. Phylogenetic analysis based on 16S rRNA gene sequences confirmed that all 60 C. difficile strains belong to the genus Clostridioides, while core-genome tree indicated that they were divided into five groups, which was consistent with the results of MLST clade analysis. All strains were confirmed to have a clindamycin antibiotic resistance gene, but the other antibiotic resistance genes differ depending on the MLST clade. Interestingly, the six strains belonging to the sequence type 17 among the nine C. difficile strains isolated here exhibited unique genomic characteristics for PaLoc and CdtLoc, the two toxin gene loci identified in this study, and harbored similar antibiotic resistance genes.ConclusionIn this study, we identified the specific genomic characteristics of Korean C. difficile strains, which could serve as basic information for CDI prevention and treatment in Korea.
| S-EPMC8447795 | biostudies-literature
Project description:BackgroundPatients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity.ObjectivesWe performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD.DesignThis is a multicentre cohort study conducted in five European FMT centres.MethodsAdult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death.ResultsIn total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years).ConclusionFMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.
| S-EPMC9998411 | biostudies-literature