Evidence map›Paper›PMID 29360463›Full record

ArticleGastroenterology2018

Ceragenin CSA13 Reduces Clostridium difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites.

Jiani Wang, Sally Ghali, Chunlan Xu, Caroline C Mussatto, Christina Ortiz, Elaine C Lee, Diana H Tran, Jonathan P Jacobs, Venu Lagishetty, Kym F Faull and 4 more

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Polymers · 2023
    Article
  8. Article
  9. Article
  10. Opportunities for Nanomedicine inAntibiotics (Basel, Switzerland) · 2021
    Review
  11. Article
  12. Article
  13. Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 2 countries.

Jiani WangCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California; Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China.
Sally GhaliCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Chunlan XuCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California; The Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xian, Shaanxi Province, China.
Caroline C MussattoCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Christina OrtizCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Elaine C LeeCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Diana H TranCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Jonathan P JacobsCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Venu LagishettyCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Kym F FaullPasarow Mass Spectrometry Laboratory, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Travis MollerPasarow Mass Spectrometry Laboratory, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Maura RossettiImmunogenetics Center, Department of Pathology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California.
Xinhua ChenDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Hon Wai KoonCenter for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California. Electronic address: hkoon@mednet.ucla.edu.
University of California, Los Angeles · USBeth Israel Deaconess Medical Center · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Role of Cathelicidin in Intestinal InflammationK01DK084256 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOON, HON WAI · 2010 to 2014
$743k
Role of Cathelicidin in Obesity and DiabetesR03DK103964 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOON, HON WAI · 2015 to 2016
$154k
NCATS NIH HHS UL1 TR001881NIDDK NIH HHS K01 DK084256NIDDK NIH HHS P30 DK041301NIDDK NIH HHS R03 DK103964
6 · The paper itself

Abstract

BACKGROUND &

aimsClostridium difficile induces intestinal inflammation by releasing toxins A and B. The antimicrobial compound cationic steroid antimicrobial 13 (CSA13) has been developed for treating gastrointestinal infections. The CSA13-Eudragit formulation can be given orally and releases CSA13 in the terminal ileum and colon. We investigated whether this form of CSA13 reduces C difficile infection (CDI) in mice.

methodsC57BL/6J mice were infected with C difficile on day 0, followed by subcutaneous administration of pure CSA13 or oral administration of CSA13-Eudragit (10 mg/kg/d for 10 days). Some mice were given intraperitoneal vancomycin (50 mg/kg daily) on days 0-4 and relapse was measured after antibiotic withdrawal. The mice were monitored until day 20; colon and fecal samples were collected on day 3 for analysis. Blood samples were collected for flow cytometry analyses. Fecal pellets were collected each day from mice injected with CSA13 and analyzed by high-performance liquid chromatography or 16S sequencing; feces were also homogenized in phosphate-buffered saline and fed to mice with CDI via gavage.

resultsCDI of mice caused 60% mortality, significant bodyweight loss, and colonic damage 3 days after infection; these events were prevented by subcutaneous injection of CSA13 or oral administration CSA13-Eudragit. There was reduced relapse of CDI after administration of CSA13 was stopped. Levels of CSA13 in feces from mice given CSA13-Eudragit were significantly higher than those of mice given subcutaneous CSA13. Subcutaneous and oral CSA13 each significantly increased the abundance of Peptostreptococcaceae bacteria and reduced the abundance of C difficile in fecal samples of mice. When feces from mice with CDI and given CSA13 were fed to mice with CDI that had not received CSA13, the recipient mice had significantly increased rates of survival. CSA13 reduced fecal levels of inflammatory metabolites (endocannabinoids) and increased fecal levels of 4 protective metabolites (ie, citrulline, 3-aminoisobutyric acid, retinol, and ursodeoxycholic acid) in mice with CDI. Oral administration of these CSA13-dependent protective metabolites reduced the severity of CDI.

conclusionsIn studies of mice, we found the CSA13-Eudragit formulation to be effective in eradicating CDI by modulating the intestinal microbiota and metabolites.

Indexed as

AnimalsAnti-Bacterial AgentsClostridioides difficileEnterocolitis, PseudomembranousFecesGastrointestinal MicrobiomeIntestinesMiceMice, Inbred C57BLSteroidsVancomycinAnti-Bacterial Agentsceragenin CSA-13SteroidsVancomycinBacteriaColitisIntestineMetabolomics

Identifiers

PMID29360463
PMCPMC5927842
OpenAlexW2782561171

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.