Carbohydrate-induced Resilience of the Gut Microbiome After Antibiotics Use

NCT ID: NCT04561284

Last Updated: 2022-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-01
• Study Completion Date: 2022-10-21

Brief Summary

The gut microbiome is a complex ecosystem with a wide range of functions, and it is thought that it can influence multiple processes in the human body. In turn, the composition and activity of the gut microbiome is affected by many factors as well.

Antibiotics can be very effective in treating bacterial infections, but they are also associated with detrimental health effects. Previous studies have already shown that antibiotics disturb the human gut microbiome composition by destroying commensal bacteria. As it is well known that the microbiome influences host metabolism, perturbation of the healthy microbiome (dysbiosis) is thought to be disease causing.

Prebiotics, on the other hand, are beneficial for the gut microbiome. These so-called indigestible fibers are naturally present in our foods, but cannot be metabolised by the human body. Many bacteria in the human gut are able to ferment these fibers and they subsequently produce beneficial products for the rest of the body. Besides this, fiber intake stimulates growth of commensal bacteria in the human gut.

Although it has become increasingly clear that prebiotics have a beneficial effect on the gut microbiome and general health, it is still unclear to which extent the beneficial effects of prebiotics supplementation occur after the gut microbiome is disturbed by antibiotics. We hypothesize that prebiotic supplementation after antibiotics use will improve restoration of the gut microbiome to a healthy state compared to placebo.

Detailed Description

In this double-blind, randomized placebo-controlled study, 40 overweight, but otherwise healthy adults will first receive vancomycin for 7 days (3x 500mg per day) to disturb the gut microbiome. They will then receive either indigestible fiber supplementation (classified) ór a placebo for the following 8 weeks. All study parameters will be assessed in two parallel groups, to which subjects will be assigned using minimization.

After initial screening, participants will be asked to visit the university for a total of 6 times during a period of 11 weeks. A clinical investigation day will take place at baseline, after antibiotics use and after the supplementation period. The remaining 3 visits will be short visits during the supplementation period (week 2, 4 & 6 of supplementation). Participants will be asked to collect feces every day before the university visits.

During the clinical investigation days, an abdominal subcutaneous adipose tissue will be taken under fasting conditions. Participants will also perform a 7-point oral glucose tolerance test to assess their insulin sensitivity. Furthermore, blood samples will be taken in the fasted state to assess markers of fat metabolism, short-chain fatty acids, gut hormones and inflammatory markers. Participants will be asked to hand in collected feces and to fill in questionnaires regarding stool consistency, stool frequency and physical activity. Lastly, they will be asked to hand in filled-in 3-day food diaries.

On the 3 remaining visits during the supplementation period, participants will hand in collected feces and food diaries, and fill in the questionnaires.

For these 6 visits, participants will have to invest approximately 14 hours.

Conditions

Overweight and Obesity; Insulin Resistance; Dysbiosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Indigestible fiber supplementation

Participants will receive an indigestible fiber supplementation (classified) for a period of 8 weeks. Thrice daily, they will take the fiber powder during their meals.

Group Type: EXPERIMENTAL

Indigestible fiber (classified)

Intervention Type: DIETARY_SUPPLEMENT

Participants will be asked to ingest 12 grams of indigestible fiber powder per day for a period of 8 weeks. Three times daily, they will take 4 grams of powder with their meal.

Placebo supplementation

Participants will receive placebo supplementation (Maltodextrin) for a period of 8 weeks. Thrice daily, they will take the fiber powder during their meals. The amount of maltodextrin taken will be isocaloric with the amount of indigestible fiber.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Participants will be asked to ingest 6 grams of placebo powder per day for a period of 8 weeks. Three times daily, they will take 2 grams of powder with their meal.

Interventions

Indigestible fiber (classified)

Participants will be asked to ingest 12 grams of indigestible fiber powder per day for a period of 8 weeks. Three times daily, they will take 4 grams of powder with their meal.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Participants will be asked to ingest 6 grams of placebo powder per day for a period of 8 weeks. Three times daily, they will take 2 grams of powder with their meal.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Overweight or obese (BMI: 25 - 35 kg/m^2)
• Caucasian
• Stable body weight (< 3 kg change) for the last 3 months

Exclusion Criteria

• Known allergic reaction to vancomycin or other glycopeptide antibiotics;
• Pre-diabetes, diabetes mellitus, cardiovascular disease, kidney disease, hearing disorders, cancer, asthma or bronchitis, liver malfunction, diseases affecting glucose tolerance, major illness with a life expectancy < 5 years, gastrointestinal disease or abdominal surgery;
• Abuse of products; alcohol and drugs, excessive nicotine use (> 20 cigarettes per day);
• Regular use of laxation products;
• Use of antibiotics in the past 3 months;
• Regular supplementation of pre- or probiotic products, use of pre- or probiotics 3 months prior to the start of the study;
• Plans to lose weight or currently following a hypocaloric diet;
• Following a vegetarian diet;
• Participation in organized sports activities for > 3 hours per week;
• Suffering from hearing loss or other hearing problems;
• Currently pregnant, planning to become pregnant, or currently breastfeeding.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ellen E Blaak, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Human Biology, Maastricht University

Locations

Department of Human Biology, Maastricht University Medical Centre

Maastricht, , Netherlands

Countries

Netherlands

Other Identifiers

NL73140.068.20 / METC20-025

Identifier Type: -

Identifier Source: org_study_id