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Dietary intake of galacto-oligosaccharides (GOS) may have beneficial effects on host health by affecting the microbiota composition and -activity. So far studies focused on analyses in fecal samples, while the primary site of carbohydrate fermentation is the proximal colon. To date, no studies have been performed in humans on the more proximal microbiota and the impact of fermentable carbohydrates. Further insights on the more proximal colonic microbiota would aid to targeted approaches to improve intestinal health. Therefore, we aim to study the effect of GOS on the intestinal microbiota composition and -activity in healthy adults, by sampling the more proximal human colon in a physiological condition. The primary objective of this study is to investigate the impact of four weeks GOS supplementation on intestinal microbiota composition and -activity, by sampling the proximal part of the human colon in a physiological condition. Furthermore, this study has four secondary objectives: First, to compare the intestinal microbiota composition and -activity of the proximal colon vs. distal colon at baseline and after four weeks GOS supplementation. Second, compare the luminal microbiota composition vs. mucosa adherent microbiota composition of the proximal vs. distal colon at baseline and after four weeks GOS supplementation. Third, monitor the effects of four weeks GOS supplementation on gastrointestinal symptoms. The study conforms to a randomized, double-blind, placebo-controlled, parallel design. Study population includes healthy human volunteers (male and female), 18-50 years of age. One intervention arm will include 7.2 grams of Vivinal® GOS Powder three times daily for four weeks. The other intervention arm subjects will receive placebo product (7.2 grams maltodextrin) three times daily for four weeks. At the start and end of the intervention period, several measurements will take place. The main study parameter is the change in microbial composition and -activity induced by GOS intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Galacto-oligosacchardies | Experimental | During this period subjects will receive 7.2 grams of Vivinal GOS supplements three times daily for four weeks |
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| Maltodextrin | Placebo Comparator | During this period subjects will receive 7.2 grams of maltodextrin three times daily for four weeks |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Galacto-oligosaccharides | Dietary Supplement | During this period subjects will receive 7.2 grams of Vivinal GOS supplements three times daily for four weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| Microbial composition, as determined by state of the art (e.g. HiSeq) sequencing of 16S rRNA genes in colonic luminal/fecal samples and biopsies. | Total DNA will be extracted from fecal, small intestinal fluid and biopsy samples using the repeated bead-beating method. This method has been optimized and standardized for the extraction of total bacterial DNA from human fecal samples. Isolated DNA will be used for amplification of the V4 region of the collective 16S rRNA genes using barcoded primers, while fecal and intestinal DNA as target. Afterwards, the NG-Tax pipeline will be used for microbiota profiling. A variety of programs, such as R, and in house scripts will be used for bioinformatics analyses and multivariate statistics. | Change from baseline to four weeks supplementation |
| Microbial activity as determined by metatranscriptomics using RNA in colonic luminal samples and biopsies. | Microbiota activity profiling will be performed by metatranscriptomics. In short, RNA will be isolated from the luminal samples, followed by removal of rRNA and subsequent conversion of residual RNA into cDNA. The cDNA will serve as target for paired-end HiSeq sequencing. Obtained sequence reads will be phylogenetically and functionally annotated as described before. Dedicated R-scripts as well as programs such as iPath will be used for bioinformatic analyses, including metabolic mapping, and interpretation to determine which bacterial group is performing what activities. In addition, key metabolites of saccharolytic and protein fermentation (such as (branched) chain fatty acids) will be assessed by High-performance liquid chromatography (HPLC). | Change from baseline to four weeks supplementation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| D. Keszthelyi, MD, PhD | Maastricht University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University Medical Center | Maastricht | Limburg | 6229 HX | Netherlands |
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| ID | Term |
|---|---|
| C008315 | maltodextrin |
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| Maltodextrin | Dietary Supplement | During this period subjects will receive 7.2 grams of maltodextrin supplements three times daily for four weeks |
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