Carbohydrate-induced Resilience of the Gut Microbiome After Antibiotics Use

NCT04561284 | Completed DMC

• 1 other identifier: NL73140.068.20 / METC20-025
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Overweight and Obesity; Insulin Resistance; Dysbiosis

Outcome Measures

Primary Outcomes (4)

• Gut microbiota composition

  Fecal samples will be collected at baseline, week 1, 3, 5, 7 and 9. Microbial DNA will be extracted, and microbiota composition will be analyzed by next-generation sequencing. Gut microbiota composition at week 1 will be compared with baseline to assess the effect of antibiotic use. Microbial composition during the supplementation period (week 3, 5, 7 \& 9) will be compared between the two study arms to assess restorative potential of the indigestible fiber.

  Change in gut microbiota composition after antibiotic use (week 1) compared to baseline & change in microbial composition during fiber supplementation (week 3, 5, 7 & 9) compared to placebo.

• Gut microbiota activity

  Fecal samples will be collected at baseline, week 1, 3, 5, 7 and 9. Microbial proteins will be analyzed by mass spectrometry (MS) after extraction. Gut microbiota activity at week 1 will be compared with baseline to assess the effect of antibiotic use. Microbial activity during the supplementation period (week 3, 5, 7 \& 9) will be compared between the two study arms to assess restorative potential of the indigestible fiber.

  Change in gut microbiota activity after antibiotic use (week 1) compared to baseline & change in microbial activity during fiber supplementation (week 3, 5, 7 & 9) compared to placebo.

• Fecal Short-Chain Fatty Acids (SCFA)

  Fecal samples will be collected at baseline, week 1, 3, 5, 7 and 9. Fecal SCFA levels will be analyzed using gas-chromatography MS. Fecal SCFA levels at week 1 will be compared with baseline levels to assess the effect of antibiotic use. SCFA levels in feces during the supplementation period (week 3, 5, 7 \& 9) will be compared between the two study arms to assess restorative potential of the indigestible fiber.

  Change in fecal SCFA levels after antibiotic use (week 1) compared to baseline & change in fecal SCFA levels during fiber supplementation (week 3, 5, 7 & 9) compared to placebo.

• Resistome analysis

  Fecal samples will be collected at baseline, week 1, 3, 5, 7 and 9. Microbial DNA will be extracted, and resistome analysis will be performed via qPCR, targeting specific antibiotic resistance genes (ARG). Presence of ARG at week 1 will be compared with baseline to assess the effect of antibiotic use. ARG presence during the supplementation period (week 3, 5, 7 \& 9) will be compared between the two study arms to assess the effect of the indigestible fiber.

  Change in ARG presence after antibiotic use (week 1) compared to baseline & change in ARG presence during fiber supplementation (week 3, 5, 7 & 9) compared to placebo.

Secondary Outcomes (8)

• Body Mass Index

  Change in BMI after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.

• Insulin sensitivity

  Change in insulin sensitivity after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.

• Plasma markers of fat metabolism

  Change in markers of fat metabolism after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.

• Adipose tissue gene expression

  Change in adipose tissue gene expression after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.

• Adipose tissue protein levels

  Change in adipose tissue protein levels after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.

Other Outcomes (4)

• Dietary intake

  Comparing dietary intake at week 1, 3, 5, 7 & 9 with baseline.

• Physical activity

  Comparing physical activity at week 1, 3, 5, 7 & 9 with baseline.

• Stool consistency

  Comparing stool consistency at week 1, 3, 5, 7 & 9 with baseline.

Study Arms (2)

Indigestible fiber supplementation

EXPERIMENTAL

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.

Dietary Supplement: Indigestible fiber (classified)

Placebo supplementation

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo

Interventions

Indigestible fiber (classified) 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.

Indigestible fiber supplementation

Placebo 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.

Placebo supplementation

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Department of Human Biology, Maastricht University Medical Centre

Maastricht, 6200MD, Netherlands

Location

MeSH Terms

Conditions

Overweight; Obesity; Insulin Resistance; Dysbiosis

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Pathologic Processes

Study Officials

• Ellen E Blaak, Prof. Dr.

  Department of Human Biology, Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 23, 2020
• Study Start: November 1, 2020
• Primary Completion: October 21, 2022
• Study Completion: October 21, 2022
• Last Updated: December 28, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)