Temporal Gut Microbial Changes Predict Recurrent Clostridiodes Difficile Infection in Patients With and Without Ulcerative Colitis.
Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents
/ therapeutic use
Clostridioides difficile
Clostridium Infections
/ drug therapy
Colitis, Ulcerative
/ microbiology
Feces
/ microbiology
Female
Gastrointestinal Microbiome
/ physiology
Humans
Logistic Models
Male
Middle Aged
Prospective Studies
RNA, Ribosomal, 16S
/ analysis
Recurrence
Symptom Flare Up
Young Adult
Clostridiodes difficile infection
Lasso regression
gut microbiota
predictive modeling
ulcerative colitis
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
23 10 2020
23 10 2020
Historique:
received:
14
10
2019
pubmed:
24
1
2020
medline:
21
10
2021
entrez:
24
1
2020
Statut:
ppublish
Résumé
Ulcerative colitis (UC) carries an increased risk of primary and recurrent Clostridiodes difficile infection (rCDI), and CDI is associated with UC flares. We hypothesized that specific fecal microbial changes associate with UC flare and rCDI. We conducted a prospective observational cohort study of 57 patients with UC and CDI, CDI only, and UC only. Stool samples were collected at baseline, at the end of antibiotic therapy, and after reconstitution for 16S rRNA sequencing. The primary outcomes were recurrent UC flare and rCDI. Logistic regression and Lasso models were constructed for analysis. There were 21 (45.7%) patients with rCDI, whereas 11 (34.4%) developed UC flare. Patients with rCDI demonstrated significant interindividual (P = 0.008) and intraindividual differences (P = 0.004) in community structure by Jensen-Shannon distance (JSD) compared with non-rCDI. Two cross-validated Lasso regression models predicted risk of rCDI: a baseline model with female gender, hospitalization for UC in the past year, increased Ruminococcaceae and Verrucomicrobia, and decreased Eubacteriaceae, Enterobacteriaceae, Lachnospiraceae, and Veillonellaceae (AuROC, 0.94); and a model 14 days after completion of antibiotics with female gender, increased Shannon diversity, Ruminococcaceae and Enterobacteriaceae, and decreased community richness and Faecalibacterium (AuROC, 0.9). Adding JSD between baseline and post-treatment samples to the latter model improved fit (AuROC, 0.94). A baseline model including UC hospitalization in the past year and increased Bacteroidetes was associated with increased risk for UC flare (AuROC, 0.88). Fecal microbial features at baseline and after therapy predict rCDI risk in patients with and without UC. These results may help risk stratify patients to guide management.
Sections du résumé
BACKGROUND
Ulcerative colitis (UC) carries an increased risk of primary and recurrent Clostridiodes difficile infection (rCDI), and CDI is associated with UC flares. We hypothesized that specific fecal microbial changes associate with UC flare and rCDI.
METHODS
We conducted a prospective observational cohort study of 57 patients with UC and CDI, CDI only, and UC only. Stool samples were collected at baseline, at the end of antibiotic therapy, and after reconstitution for 16S rRNA sequencing. The primary outcomes were recurrent UC flare and rCDI. Logistic regression and Lasso models were constructed for analysis.
RESULTS
There were 21 (45.7%) patients with rCDI, whereas 11 (34.4%) developed UC flare. Patients with rCDI demonstrated significant interindividual (P = 0.008) and intraindividual differences (P = 0.004) in community structure by Jensen-Shannon distance (JSD) compared with non-rCDI. Two cross-validated Lasso regression models predicted risk of rCDI: a baseline model with female gender, hospitalization for UC in the past year, increased Ruminococcaceae and Verrucomicrobia, and decreased Eubacteriaceae, Enterobacteriaceae, Lachnospiraceae, and Veillonellaceae (AuROC, 0.94); and a model 14 days after completion of antibiotics with female gender, increased Shannon diversity, Ruminococcaceae and Enterobacteriaceae, and decreased community richness and Faecalibacterium (AuROC, 0.9). Adding JSD between baseline and post-treatment samples to the latter model improved fit (AuROC, 0.94). A baseline model including UC hospitalization in the past year and increased Bacteroidetes was associated with increased risk for UC flare (AuROC, 0.88).
CONCLUSION
Fecal microbial features at baseline and after therapy predict rCDI risk in patients with and without UC. These results may help risk stratify patients to guide management.
Identifiants
pubmed: 31971239
pii: 5714595
doi: 10.1093/ibd/izz335
pmc: PMC7755141
doi:
Substances chimiques
Anti-Bacterial Agents
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1748-1758Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002241
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034933
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI124255
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
Sci Rep. 2016 May 11;6:25945
pubmed: 27166072
Genome Med. 2016 Jul 13;8(1):75
pubmed: 27412252
Inflamm Bowel Dis. 2016 Jul;22(7):1744-54
pubmed: 27120571
Clin Infect Dis. 2012 Aug;55 Suppl 2:S93-103
pubmed: 22752871
Cell Mol Gastroenterol Hepatol. 2016 Mar 03;2(4):468-481
pubmed: 27795980
Aliment Pharmacol Ther. 2016 Oct;44(7):715-727
pubmed: 27481036
Am J Gastroenterol. 2016 Aug;111(8):1141-6
pubmed: 27215924
Int J Syst Evol Microbiol. 2016 Dec;66(12):5575-5599
pubmed: 27620848
Microb Ecol. 2008 Oct;56(3):395-402
pubmed: 18209965
mBio. 2014 May 06;5(3):e01021-14
pubmed: 24803517
Cell Host Microbe. 2018 Oct 10;24(4):600-610.e4
pubmed: 30308161
Nature. 2011 May 12;473(7346):174-80
pubmed: 21508958
Anaerobe. 2016 Aug;40:95-9
pubmed: 27370902
J Stat Softw. 2010;33(1):1-22
pubmed: 20808728
Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44
pubmed: 17368233
Appl Environ Microbiol. 2009 Dec;75(23):7537-41
pubmed: 19801464
Am J Gastroenterol. 2008 Jun;103(6):1443-50
pubmed: 18513271
Gut Microbes. 2011 May-Jun;2(3):145-58
pubmed: 21804357
Microbiome. 2013 Jan 09;1(1):3
pubmed: 24467987
Genome Med. 2016 Apr 27;8(1):47
pubmed: 27121861
Infect Immun. 1984 Jul;45(1):185-91
pubmed: 6735467
J Clin Invest. 2014 Oct;124(10):4182-9
pubmed: 25036699
Microbiome. 2017 Nov 13;5(1):148
pubmed: 29132405
Clin Infect Dis. 2018 Mar 19;66(7):e1-e48
pubmed: 29462280
Inflamm Bowel Dis. 2011 Apr;17(4):976-83
pubmed: 20824818
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Nat Microbiol. 2017 Feb 13;2:17004
pubmed: 28191884
Inflamm Bowel Dis. 2011 Jan;17(1):50-5
pubmed: 20722068
Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19
pubmed: 17973645
ISME J. 2019 Sep;13(9):2306-2318
pubmed: 31089259
Gut. 2008 Feb;57(2):205-10
pubmed: 17905821
Cell Host Microbe. 2014 Mar 12;15(3):382-392
pubmed: 24629344
Inflamm Bowel Dis. 2008 Dec;14(12):1660-6
pubmed: 18623174