REMBRANDT: REcovery of the MicroBiome fRom Antibiotics for Dental implanTs

Impact of Pet Contact on Antimicrobial-associated Dysbiosis and Clostridioides Difficile Infection

Antimicrobial therapy can lead to disruption of the gut microbiome and infection with Clostridioides difficile, a disease associated with high morbidity and mortality, particularly among the elderly. Drawing on observations that pet ownership and close contact with pets are protective against colonization with C. difficile and recurrence of C. difficile infection, the proposed study will test the hypothesis that microbiota that provide colonization resistance against C. difficile are shared between patients and their pets and that pet contact can mitigate antimicrobial-associated gut dysbiosis and the risk of C. difficile infection. This study will further define epidemiologic and pathophysiologic characteristics of C. difficile infection and gut microbiome dysbiosis that could enhance therapeutic options for these conditions, potentially through non-invasive interventions involving animal contact.

Study Overview

• Status: Recruiting
• Conditions: Dysbiosis; Clostridium Difficile; Antibiotic-Associated Colitis; Pet-Human Bonding

Detailed Description

Clostridioides difficile infection (CDI) is one of the most common causes of healthcare-associated infectious diarrhea and results in significant morbidity and mortality. CDI occurs when the native gut microbiome is disrupted, most often following antimicrobial therapy, and the consequent dysbiosis results in a decrease in microbial diversity, changes in abundance of certain bacterial taxa, and loss of colonization resistance against C. difficile. Restoration of a "functionally intact" gut microbiome is critical to clearing C. difficile, and inadequate restoration can lead to recurrent CDI. The recovery of the gut microbiome from dysbiosis is poorly understood, and factors associated with having and re-gaining a providing colonization resistance against C. difficile are not well known. While animal reservoirs can serve as potential sources of pathogenic bacteria, studies by the candidate and other investigators found that pet ownership protects against colonization and re-infection with C. difficile. Moreover, microbiota are shared between pets and their owners, and the microbiomes of pets contain bacterial taxa that provide colonization resistance against C. difficile. Based on these data, the proposed research will 1) test the hypothesis that the observed protective effects of pet ownership are due to sharing of microbiota that provide colonization resistance against C. difficile between pets and owners; 2) determine whether pet contact mitigates antimicrobial-associated disruption of the gut microbiome and enhances its recovery; and 3) assess whether pet contact decreases the likelihood of colonization and infection with C. difficile following antimicrobial therapy. This will be accomplished though longitudinal sampling of the gut microbiome within the patient/pet unit among patients receiving prophylactic antimicrobials for non-enteric indications (dental implants).

The study will further define epidemiologic and pathophysiologic characteristics of CDI that could enhance therapeutic options for this disease. The underlying premise that animals are a source of protective microbiota rather than a reservoir of C. difficile represents a paradigm shift in CDI epidemiology that may identify animal contact as a novel microbiome-based form of therapy.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Laurel Redding, VMD, PhD; Phone Number: 6109256307; Email: lredding@upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Robert Schattner Center, University of Pennsylvania, School of Dental Medicine
      • Contact: Marta Gabinsky; Email: mgabi@upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The source population will include patients over 18 years of age receiving prophylactic oral antimicrobials for dental implants at the University of Pennsylvania School of Dental Medicine.

Description

Inclusion Criteria:

• 18 years of age or older.
• Receiving a dental implant.
• Ability to understand study procedures and to comply with them for the entire length of the study.

Exclusion Criteria:

• Antimicrobial therapy or hospitalization in the prior three months;
• Any gastrointestinal illness or underlying pathology (e.g., Inflammatory Bowel Disease, gastric ulceration)
• Sustained diarrheal disease (i.e., at least 3 episodes of loose or watery stool per day for 3 or more days) in the prior 3 months;
• Prior history of CDI in the prior year;
• Immunomodulating medication (e.g., tumor necrosis factor inhibitors or systemic steroids) or conditions (e.g., leukemia)
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pet owner; Pet owners
Non pet owner; Non pet owners

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal change in diversity and composition of the gut microbiota following oral antibiotic prophylaxis	Changes in alpha diversity, beta diversity and composition of the gut microbiome will be ascertained between baseline (prior to taking antibiotics) and 3, 10, 30 and 90 days following the start of the antibiotic regimen	90 days
Colonization or infection with C. difficile following antibiotic prophylaxis	The presence of C. difficile in patients' stool will be determined before and 3 days after the beginning of the antibiotic regimen	3 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Laurel Redding, VMD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Enterocolitis; Enterocolitis, Pseudomembranous; Dysbiosis
• Other Study ID Numbers: 844131; 1K23AI163351-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Any data, specimens, forms, reports, video recordings, and other records that leave the site will be identified only by a participant identification number (Participant ID, PID) to maintain confidentiality. All records will be kept in a locked file cabinet. All computer entry and networking programs will be done using PIDs only. Information will not be released without written permission of the participant, except as necessary for monitoring by the IRB or NIAID.

Any presentation, abstract, or manuscript will be made available for review by the sponsor and the NIAID prior to submission.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No