Dietary Fibers Effect on the Gut Microbiota Composition

Study Overview
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Brief Summary
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The randomized double-blinded placebo-controlled multicenter study will be held in parallel groups. During 5 weeks the efficacy of different endpoints as a measure of response to the daily intake of dietary fibers (8 g of either inulin, pectin, beta-glucan or galactooligosaccharides) will be evaluated. Gut microbiota composition, lipids levels, inflammation markers, microbiome metabolites, changes in quality of life and stool parameters will be assessed in order to predict individual response in participants without serious chronic diseases

Detailed Description
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A randomized double-blinded study will include 270 volunteers without clinical manifestations of chronic diseases. Participants will be randomized into one of five arms daily consuming one of the following: placebo (maltodextrin, 8 g), inulin (8 g), pectin (8 g), beta-glucan (8 g) or oligosaccharides (8 g). The study will include a 5-day screening period and a 5-weeks intervention period. During screening stage, a volunteer will complete a questionnaire, and the following measurements will be performed: blood levels of glycated hemoglobin, creatinine, lipids, C-reactive protein, anthropometric measurements, as well as cardiovascular risk will be assessed. Before and after the intervention blood and stool samples will be collected to conduct the following analyses: an extended lipid spectrum analysis, high-sensitivity C-reactive protein, 16S rRNA gut microbiome sequencing, laboratory stool testing, stool fecal short-chain fatty acids analysis. Anthropometric measures, physical examination will be performed for each volunteer. The following questionnaires will be completed: dietary recall questionnaire, SF-36, the Rome Criteria for the Functional gastrointestinal disorders (functional constipation). The assessed scales will include Bristol stool scale, Hospital Anxiety and Depression Scale (HADS), Hamilton Rating Scale for Depression (HRSD).

Official Title
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A Randomized, Placebo-controlled, Double-blinded, Parallel-group, 5-week Study of the Dietary Fibers Intake (Inulin, Pectin, Beta-glucan, Galactooligosaccharides) Influence on the Gut Microbiota Composition and Cardiovascular Risk Factors

Conditions
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Microbiome, Metabolic Syndrome, Cardiovascular Risk Factor, Inflammation, Dyslipidemias

Intervention / Treatment
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* Dietary Supplement: Maltodextrin
* Dietary Supplement: Inulin
* Dietary Supplement: Pectin
* Dietary Supplement: Beta-glucan
* Dietary Supplement: Galactooligosaccharides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject doesn't have any active complaints Subject doesn't have any active or acute diseases at the time of enrollment Subject signed informed consent Exclusion Criteria: High or very high cardiovascular risk Levels of total cholesterol and/or low-density lipoproteins requiring immediate assignment of drug treatment (according to ESC Guidelines for the management of dyslipidaemias, 2019) Diabetes mellitus of any type HbA1с of 5,7% or higher Obesity requiring medical therapy or surgery (according to European Guidelines for Adult Obesity Management, 2019) Gastrointestinal diseases in history including ulcerative colitis, Crohn's disease, celiac disease, gallbladder disease (calculous cholecystitis, cholangitis, etc.) not related to functional disorders; liver or pancreas diseases Irritable bowel syndrome, abdominal pain of any location and etiology Pain syndrome of any localization Flatulence Oncology diseases Mental disorders Rheumatoid arthritis or other autoimmune diseases Acute infectious diseases or exacerbation of any diseases Recent (<3 months) administration of proton pump inhibitors, antimicrobial therapy or surgical intervention Recent (<3 weeks) use of probiotics, antacids, nonsteroidal anti-inflammatory drugs, laxatives Pregnancy, planning to be pregnant or breast feeding at any point during the study or study enrollment Current alcohol/drug abuse (more than 3 points for women and 4 for men according to AUDIT-C questionnaire and/or more than 7 points on the AUDIT questionnaire) or addiction therapy within 12 months prior to screening Allergies to any prebiotic or placebo ingredients Planned relocation from the home region during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Maltodextrin<br>Within first 6 days, there will be an increase in the fiber dose: 1st and 2nd days - 2g, 3rd and 4th - 4g per day, 5th and 6th - 6g per day. Starting from the 7th and till the 35th day - 8g per day. Placebo will be given in a powder form to be added to 250 ml of water. | Dietary Supplement: Maltodextrin<br>* NOVAPRODUKT, white powder 5 weeks intervention<br>|
| Experimental: Inulin<br>Within first 6 days, there will be an increase in the fiber dose: 1st and 2nd days - 2g, 3rd and 4th - 4g per day, 5th and 6th - 6g per day. Starting from the 7th and till the 35th day - 8g per day. Placebo will be given in a powder form to be added to 250 ml of water. | Dietary Supplement: Inulin<br>* BENEO-Orafti, white powder 5 weeks intervention<br>|
| Experimental: Pectin<br>Within first 6 days, there will be an increase in the fiber dose: 1st and 2nd days - 2g, 3rd and 4th - 4g per day, 5th and 6th - 6g per day. Starting from the 7th and till the 35th day - 8g per day. Placebo will be given in a powder form to be added to 250 ml of water. | Dietary Supplement: Pectin<br>* BANG & BONSOMER GROUP OY, white powder 5 weeks intervention<br>|
| Experimental: Beta-glucan<br>Within first 6 days, there will be an increase in the fiber dose: 1st and 2nd days - 2g, 3rd and 4th - 4g per day, 5th and 6th - 6g per day. Starting from the 7th and till the 35th day - 8g per day. Placebo will be given in a powder form to be added to 250 ml of water. | Dietary Supplement: Beta-glucan<br>* Tate & Lyle, white powder 5 weeks intervention<br>|
| Experimental: Galactooligosaccharides<br>Within first 6 days, there will be an increase in the fiber dose: 1st and 2nd days - 2g, 3rd and 4th - 4g per day, 5th and 6th - 6g per day. Starting from the 7th and till the 35th day - 8g per day. Placebo will be given in a powder form to be added to 250 ml of water. | Dietary Supplement: Galactooligosaccharides<br>* FrieslandCampina, white powder 5 weeks intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood lipids levels | LDL, HDL, TC, TG, apoB, Lp(a) | Change from Baseline Blood lipids levels at 5th week | 
| Change in Gut microbiota composition | Relative abundance of bacterial taxa according to 16S rRNA sequencing data | Change from Baseline at 5th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fecal short-chain fatty acids | Butyrate, propionate and acetate concentrations | Change from Baseline at 5th week | 
| Change in High sensitive C-reactive protein | Low-grade inflammation assessment | Change from Baseline at 5th week | 
| Change in Stool consistency | The Bristol stool scale is a diagnostic medical tool designed to classify the form of human faeces into seven categories. | Change from Baseline at 5th week | 
| Change in Stool frequency | Rome criteria questionnaire. The Rome IV criteria for the diagnosis of irritable bowel syndrome require that patients have had recurrent abdominal pain on average at least 1 day per week during the previous 3 months that is associated with two or more of the following : Related to defecation (may be increased or unchanged by defecation) | Change from Baseline at 5th week | 
| Change in Body Composition | Bioelectrical impedance analysis | Baseline and 5th week | 
| Change in Quality of Life: SF-36 questionnaire | According to SF-36 questionnaire The Medical Outcomes Short-Form 36-Item Health Survey (SF-36) It is a self-administered questionnaire comprising 36-items measuring eight dimensions of general HRQOL: physical functioning (10 items), role limitation due to physical health problems (4 items), bodily pain (2 items), general health perceptions (5 items), vitality (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and general mental health (5 items). In addition to scores for individual dimensions, two summary scores assessing physical and mental dimensions of health and well-being can also be calculated: Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score, respectively | Change from Baseline at 5th week | 
| Change in Psychological distress | Hospital Anxiety and Depression Scale (HADS) Patients anxiety and depression will be assessed using the HADS : Hospital Anxiety and Depression scale. Scores of the HADS scale can be defined as: By adding the points of the answers: 1, 3, 5, 7, 9, 11, 13: we obtain the Total A which corresponds to the measure of the anxiety, then: 7 or less: absence of symptomatology; 8 to 10: doubtful symptomatology; 11 and above: certain symptomatology. By adding the points of the answers: 2, 4, 6, 8, 10, 12, 14: we obtain the Total B which corresponds to the measure of the depression, then: 7 or less: absence of symptomatology; 8 to 10: doubtful symptomatology; 11 and above: certain symptomatology. The minimal score is 0 and the maximal total score is 42. | Change from Baseline at 5th week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary fiber, Gut Microbiota, Cardiovascular risk factors, Lipid metabolism