Dataset Information

Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.

ABSTRACT: Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD + CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD + CDI, comparing longitudinal data on the gut microbiome, metabolome, and other measures. The microbiome is dysbiotic and heterogeneous in both disease states, but the metabolome reveals disease-specific patterns. The IBD group shows increased concentrations of markers of inflammation and tissue damage compared with healthy controls, and metabolic changes associate with susceptibility to CDI. In IBD + CDI, we detect both metabolites associated with inflammation/tissue damage and fermentation products produced by C. difficile. The most discriminating metabolite found is isocaproyltaurine, a covalent conjugate of a distinctive C. difficile fermentation product (isocaproate) and an amino acid associated with tissue damage (taurine), which may be useful as a joint marker of the two disease processes.

SUBMITTER: Bushman FD

PROVIDER: S-EPMC9332131 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.

Bushman Frederic D FD Conrad Maire M Ren Yue Y Zhao Chunyu C Gu Christopher C Petucci Christopher C Kim Min-Soo MS Abbas Arwa A Downes Kevin J KJ Devas Nina N Mattei Lisa M LM Breton Jessica J Kelsen Judith J Marakos Sarah S Galgano Alissa A Kachelries Kelly K Erlichman Jessi J Hart Jessica L JL Moraskie Michael M Kim Dorothy D Zhang Huanjia H Hofstaedter Casey E CE Wu Gary D GD Lewis James D JD Zackular Joseph P JP Li Hongzhe H Bittinger Kyle K Baldassano Robert R

Cell host & microbe 20200820 3

Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD + CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD + CDI, comparing longitudinal data on the gut microbiome, metabolome, and other measures. The microbiome is dysbiotic and heterogeneous in both disease states, but the metabolome reveals di ...[more]

PMID: 32822584

Similar Datasets

Project description:Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen. Conditional and joint multi-SNP analyses were used to identify independent associations. Imputation of the human leukocyte antigen (HLA) region with fine mapping was used to try to identify causal HLA allele groups. Two-sample bidirectional Mendelian randomization (MR) was implemented to determine causal relationships between IBD and CDI. A total of 3,500 cases of CDI and 674,323 controls were meta-analyzed, revealing one genome-wide significant variant for CDI, HLA-C;LINC02571-rs3134745-C (P = 4.27E-08), which annotated to the major histocompatibility complex on chromosome 6. While fine mapping did not identify a statistically significant HLA allele group, there was a suggestive signal for HLA-B*35:01 (P = 4.74e-04). Using two-sample MR, genetically predicted IBD was associated with increased risk of CDI (MR Egger [odds ratio {OR} 1.16, 95% confidence interval {CI} 1.02-1.31]). Subset analysis revealed that risk was primarily driven by genetically predicted ulcerative colitis (MR Egger [OR 1.22, 95% CI 1.05-1.41]). These results highlight the importance of the host immune response in CDI pathogenesis, help explain the observed relationship between IBD and CDI, and open new avenues for targeted treatment of CDI in IBD.IMPORTANCEData from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.

Dataset Information

Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.

Publications

Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets