Clinical trial NCT04561284: Carbohydrate-induced Resilience of the Gut Microbiome After Antibiotics Use
Official title: Carbohydrate-induced Resilience of the Gut Microbiome After Antibiotics Use
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight and Obesity
Insulin Resistance
Dysbiosis
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2020-09-23
Enrollment: 39
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Gut microbiota composition
timeFrame: 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.
measure: Gut microbiota activity
timeFrame: 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.
measure: Fecal Short-Chain Fatty Acids (SCFA)
timeFrame: 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.
measure: Resistome analysis
timeFrame: 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:
measure: Body Mass Index
timeFrame: Change in BMI after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Insulin sensitivity
timeFrame: Change in insulin sensitivity after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Plasma markers of fat metabolism
timeFrame: Change in markers of fat metabolism after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Adipose tissue gene expression
timeFrame: Change in adipose tissue gene expression after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Adipose tissue protein levels
timeFrame: Change in adipose tissue protein levels after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Plasma short chain fatty acids
timeFrame: Change in plasma SCFA levels after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Inflammatory markers
timeFrame: Change in plasma inflammatory marker levels after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
measure: Gut hormones
timeFrame: Change in plasma gut hormone levels after 1 week of antibiotic use compared to baseline & after 8-week indigestible fiber supplementation compared to placebo.
Other outcomes:
measure: Dietary intake
timeFrame: Comparing dietary intake at week 1, 3, 5, 7 & 9 with baseline.
measure: Physical activity
timeFrame: Comparing physical activity at week 1, 3, 5, 7 & 9 with baseline.
measure: Stool consistency
timeFrame: Comparing stool consistency at week 1, 3, 5, 7 & 9 with baseline.
measure: Gastrointestinal symptoms
timeFrame: Comparing gastrointestinal symptoms at week 1, 3, 5, 7 & 9 with baseline.
Locations:
city: Maastricht
country: Netherlands
facility: Department of Human Biology, Maastricht University Medical Centre
Study officials:
affiliation: Department of Human Biology, Maastricht University
name: Ellen E Blaak, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: