Dietary Interventions and Butyrate Production in Behçet's Patients

Study Overview
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Brief Summary
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A dietary intervention trial will be performed on patients affected by Behçet's syndrome. Three different diets will be compared, analyzing their effects on the gut microbiota composition, on endogenous butyrate production and on the general symptoms in Behçet's patients.

Detailed Description
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A dietary intervention trial will be conducted with the use of three different diets in order to compare the effects of these diets on the gut microbiota composition, on endogenous butyrate production and on the general symptoms in Behçet's patients. The study will be a randomized, open trial designed to test whether a vegetarian diet or an habitual diet supplemented with oral butyrate would benefit the butyrate production, the gut microbiota composition and the general symptoms of Behçet's patients, compared with the habitual diet. The study will involve 30 subjects with Behçet syndrome. Patients will be randomly assigned to follow a 3-months isocaloric dietary profile with either: vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products habitual diet supplemented with 2.4g/day of oral butyrate habitual diet without supplementation At the baseline visit, subjects will be educated about the aims and methods of the clinical trial and will sign their informed consent form. Anthropometric measurements, body composition, and blood and stool sampling will be obtained from each participant at the beginning and at the end of the intervention period. All subjects will be examined between 07.00 and 09.30 hours after a 12 h fasting period. The following parameters will be analyzed both at the beginning and at the end of the intervention period: Complete blood count Lipid variables - total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides Glycemic profile - glucose, insulin, glycated hemoglobin (HbA1C), HOMA index Liver function tests - aspartate aminotransferase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin Kidney function tests - serum creatinine, urea, uric acid Mineral profile - sodium, potassium, magnesium, calcium Iron metabolism - iron, ferritin Vitamin profile - vitamin B12, folic acid, vitamin D Thyroid function - TSH Inflammatory markers - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA) Serology for celiac disease - IgA, anti-transglutaminase antibodies (IgA), anti endomysium antibodies (IgA) Circulating levels of inflammatory cytokines Oxidative stress markers Gut microbiota composition Butyrate production At the beginning and at the end of the intervention period, participants will be asked to complete a questionnaire, which will assess Behçet's symptoms frequency and severity. In addition, participants will be contacted by phone to complete a 24-hours recall in order to test the adherence to diets they have been assigned to.

Official Title
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Therapeutic Modulation of Butyrate Production in Behçet's Patients: a Dietary Intervention Trial

Conditions
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Behcet Syndrome

Intervention / Treatment
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* Dietary Supplement: Oral butyrate
* Dietary Supplement: Vegetarian diet
* Dietary Supplement: Habitual diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients affected by Behçet's disease Exclusion Criteria: Pregnancy or breastfeeding Presence of diabetes mellitus Presence of other immune-mediated diseases Presence or history of cancer in the last 5 years Presence of infectious diseases in the last 3 months No antibiotic therapy in the last 3 months No vegetarian or vegan diet No intake of pro- or pre-biotics in the last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Behçet's will be assigned to one of the following treatments: vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products habitual diet supplemented with 2.4g/day of oral butyrate habitual diet without supplementation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vegetarian diet<br>vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products | Dietary Supplement: Vegetarian diet<br>* Patients follow a vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products<br>|
| Experimental: Habitual diet + oral butyrate<br>habitual diet supplemented with 2.4g/day of oral butyrate | Dietary Supplement: Oral butyrate<br>* Patients follow the habitual diet supplemented with 2.4g/day of oral butyrate<br>|
| Active Comparator: Habitual diet<br>habitual diet without supplementation | Dietary Supplement: Habitual diet<br>* Patients follow the habitual diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of gut microbiota composition |  | 0-3 months | 
| Evaluation of butyrate production | For the extraction of SCFAs (and butyrate in particular) the method described in Schnorr et al. will be follow [Schnorr SL, Candela M, Rampelli S, Centanni M, Consolandi C, Basaglia G,et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun 2014;5:3654] | 0-3 months | 
| Complete blood count | composite score | 0-3 months | 
| Lipid variables | composite score taking into account the levels of: total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides | 0-3 months | 
| Glycemic profile | composite score taking into account the levels of : glucose, insulin, glycated hemoglobin (HbA1C), HOMA index | 0-3 months | 
| Vitamin profile | composite score, taking into account the levels of: vitamin B12, folic acid, vitamin D | 0-3 months | 
| Liver function tests | composite score taking into account the levels of: aspartate aminotransferase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin | 0-3 months | 
| Kidney function tests | composite score taking into account the levels of : serum creatinine, urea, uric acid | 0-3 months | 
| Mineral profile | composite score taking into account the levels of: sodium, potassium, magnesium, calcium | 0-3 months | 
| Iron metabolism | composite score taking into account the levels of: iron, ferritin | 0-3 months | 
| Thyroid function | measurement of TSH levels | 0-3 months | 
| Inflammatory markers | composite score taking into account the levels of: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA) | 0-3 months | 
| Serology for celiac disease | composite score taking into account the levels of: IgA, anti-transglutaminase antibodies (IgA), anti endomysium antibodies (IgA) | 0-3 months | 
| Circulating levels of inflammatory cytokines | composite score | 0-3 months | 
| Oxidative stress markers | composite score | 0-3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation Behçet's symptoms frequency and severity | Participants are asked to complete a questionnaire, which will assess Behçet's symptoms frequency and severity. | 0-3 months |