Assessing the Potential Role of the Gut Microbiome in Modulating Physical Abilities in Humans

The intestinal microbiome is a microbial system that is influenced by host genetics and environmental exposures such as nutrition, stress and medications. There is a growing body of evidence indicating the significant contribution of the gut microbiome to host health and disease. Furthermore, it has been shown that exercise may modify the microbiome composition. However, important mechanistic questions related to the possible associations between exercise and the human gut microbiome remain unanswered.

In this study, the investigators are using advanced state-of-the-art measurements of physical activity level and related metabolic parameters whether there is a connection between the microbiome and physical abilities in healthy participants and whether antibiotics consumption can influence host physical abilities and glycemic responses through changes induced in microbiome composition and function.

Study Overview

• Status: Not yet recruiting
• Conditions: FMT; Physical Abilities
• Intervention / Treatment: Drug: Antibiotics; Other: Fecal Microbiota Transplantation; Other: Cellules Pills; Other: Agarose Capsules

Detailed Description

During all days of the study, participants will be connected to a continuous glucose monitor (CGM).

In the second segment of the study, participants will be randomized into two groups: antibiotics or placebo, which will be consumed for 7 days.

The third segment of the trial, participants will undergo an FMT/placebo administration for three consecutive days according to their randomization: participants who received antibiotics will receive FMT and participants who received placebo pills will receive placebo capsules in this segment as well.

During the study, participants will collect stool and buccal samples which will be used for microbiota profiling.

Furthermore, participants will undergo physical abilities test, anthropometric measurements, medical history questioners, blood and urine samples and Dual X-ray absorptiometry (DXA) test.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ilan Youngster, Dr.; Phone Number: +972-50630119; Email: youngsteri@asaf.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI<28
• Age - 20-35
• Are used to exercise in aerobic sports (running, swimming, Zumba, ball games, functional training, surfing, tennis, wrestling ext.).
• Exercise at least twice a week, for a minimum duration of the last 6 months.

Exclusion Criteria:

• Consumption of antibiotics (PO) or probiotics 3 months prior to the first day of the experiment.
• Diagnosis of type 1 or type 2 diabetes.
• Pregnancy, fertility treatments, breastfeeding women six months prior to enrollment and during the study.
• Chronic disease (e.g. AIDS, Cushing syndrome, CKD, acromegaly, hyperthyroidism etc.)
• Cancer and recent anticancer treatment
• Psychiatric disorders
• Coagulation disorders
• Gastrointestinal disorders
• Bariatric surgery
• Alcohol or substance abuse
• BMI>28
• Any physical condition precluding the completion of a routine effort test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Antibiotics + FMT; 7 days of antibiotics- Ciprofloxacin, 500 mg 2/day & Metronidazole (Flagyl), 500 mg 3/day. After antibiotics administration, participants will receive 10 aFMT capsules for three consecutive days (a total of 30 capsules).	Drug: Antibiotics; Ciprofloxacin, 500 mg 2/day & Metronidazole (Flagyl), 500 mg 3/day.; Other Names: Ciprofloxacin & Metronidazole; Other: Fecal Microbiota Transplantation; Fecal Microbiota Transplantation is the process of transferring stool from a healthy donor to another.; Other Names: FMT
PLACEBO_COMPARATOR: Placebo; 7 days of cellules pills. After cellules pills administration, participants will receive 10 agarose capsules for three consecutive days (a total of 30 capsules).	Other: Cellules Pills; 7 days of cellules placebo pills.; Other: Agarose Capsules; Placebo capsules consist a combination of agarose in normal saline/glycerol (the same vehicle as in a FMT capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome Profiling	Collection of stool and buccal samples samples for microbiome composition analysis with16s rRNA sequencing.	2 years
Body Mass Index (BMI)	The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m^2	2 years
Body Circumferences	waist, hips, and limbs (cm).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Responses	Performing continuous glucose monitor (CGM)	2 years
Bone Mineral Density (BMD)	Using Dual X-ray absorptiometry (DXA) test	2 years

Collaborators and Investigators

• Sponsor: Assaf Harofeh MC
• Collaborators: Weizmann Institute of Science
• Investigators: Principal Investigator: Ilan Youngster, Dr., Assaf-Harofeh MC, Bee'r Yaakov Israel

Publications and helpful links

General Publications

• Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O'Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Dec;63(12):1913-20. doi: 10.1136/gutjnl-2013-306541. Epub 2014 Jun 9.
• Barton W, Penney NC, Cronin O, Garcia-Perez I, Molloy MG, Holmes E, Shanahan F, Cotter PD, O'Sullivan O. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut. 2018 Apr;67(4):625-633. doi: 10.1136/gutjnl-2016-313627. Epub 2017 Mar 30.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 20, 2022
• Primary Completion (ANTICIPATED): July 20, 2022
• Study Completion (ANTICIPATED): January 20, 2023

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 22, 2021
• First Posted (ACTUAL): August 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): December 28, 2021
• Last Update Submitted That Met QC Criteria: December 27, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Metronidazole; Anti-Bacterial Agents; Ciprofloxacin
• Other Study ID Numbers: 0277-19-ASF

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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