Prebiotics and Microbiota Composition and Functionality in Rural Burkinabe Infants

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of a mixture of prebiotics included in a food supplement on microbiota diversity and functionality, and to explore its subsequent effects on linear growth velocity and morbidity.

Detailed Description
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The central role of gut microbiota in immunity and nutritional homeostasis is now acknowledged, albeit not fully understood. Gut microbiota composition imbalances have been found in malnourished children, which were not restored by nutritional interventions as currently conducted. Therefore, the necessity to design more complete nutritional interventions that include gut health has been advised by expert committees. Prebiotics are compound that selectively enhance the growth of beneficial gut bacteria. They have been recommended and used in infant formula and weaning cereals resulting in gut microbiota resembling that of breastfed infants in formula fed infants in developed countries. A healthy gut microbiota was shown to be associated with enhanced growth patterns and decreased morbidity in children in developed countries. Evidence of such outcome is lacking in developing countries, yet such results would be particularly valuable for children from these settings, living in rather poor sanitary conditions in an environment characterized with high infectious disease load, conditions that mostly explain the high prevalence of chronic malnutrition. This study aims to assess the effect of a 6 months' supplementation with a lipid based nutrient supplement fortified with fructo-oligosaccharides and inulin on microbiota diversity and functionality in rural Burkinabe infants, and to explore its subsequent effects on linear growth velocity and morbidity.

Official Title
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Effect of Supplementation With LNS Fortified With a Mixture of FOS and Inulin on Gut Microbiota Diversity and Functionality and Its Repercussion on Growth and Morbidity During Infancy in Rural Burkina Faso

Conditions
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Growth Retardation, Infant Morbidity

Intervention / Treatment
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* Dietary Supplement: Fortified lipid based nutrient supplement
* Dietary Supplement: lipid based nutrient supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6-6.5 month old infants Weight for height and height for age z-score above -2 Permanent resident of the area and not intending to move for the next 6 months for more than a week No chronic antibiotic treatment Exempt of any current serious illness Still breastfed. Exclusion Criteria: Moderate or severe malnutrition (weight for height or height for age z-score below -2) non-permanent residence in the study area, the presence of any congenital anomalies in the child or mental/physical disease of the mother that can interfere with child feeding a chronic antibiotic treatment i.e. more than 6 weeks treatment at the time of enrolment a history of allergy to a constituent of the supplement a serious current illness

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 26 Weeks

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fortified lipid based nutrient supplement<br>lipid based nutrient supplement (Nutributter) fortified with fructo-oligosaccharides and inulin | Dietary Supplement: Fortified lipid based nutrient supplement<br>* 6 months intervention: participant will take a daily dose of 20g supplement. The product contains 3 g of a mixture (1:1) of inulin and fructan-oligosaccharide<br>|
| Active Comparator: lipid based nutrient supplement<br>lipid based nutrient supplement (Nutributter) | Dietary Supplement: lipid based nutrient supplement<br>* Dietary Supplement: lipid based nutrient supplement (Nutributter) 6 months intervention: participant will take a daily dose of 20g supplement.<br>|
| No Intervention: non intervention group<br>This group will not be supplemented | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal microbiota range-weighted richness | Composition of fecal microbiota will be determined by Illumina sequencing from which range-weighted richness will be calculated | 6 months | 
| Mean concentration of short-chain fatty acids in stool | Concentration of short-chain fatty acids (acetate, butyrate and propionate) will be measured by Gas Chromatography | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of digestive intolerance symptoms (flatulence, abdominal pain, regurgitation, vomiting, or diarrhea) | Digestive intolerance symptoms will be recalled. | once every week during the first month of supplementation | 
| Stool consistency | Stool consistency will be recalled | Once every week during the first month of supplementation | 
| Stool frequency per day | Stool frequency per day will be recalled. | 6 months | 
| Mean stool pH | Stool pH will be measured once a week with pH sticks by a study nurse | once every week during the first month of supplementation | 
| Calprotectin concentration in stool | Concentration of calprotectin will be measured by ELISA | at inclusion, 3 months and 6months after inclusion | 
| Infant linear growth velocity | Linear growth velocity will be determined using the difference between 2 length measures over the follow up time in months and expressed in millimeters/ month | once a month during 6 months | 
| Infant ponderal growth velocity | Ponderal growth velocity will be determined using the difference between 2 weight measures over the follow up time in month and expressed in grams/ month. Infant's weight will be measured at inclusion and once a month during 6 months | once a month during 6 months | 
| Cumulative morbidity | Cumulative morbidity of (malaria, gastro-intestinal tract infection, acute respiratory tract infection, acute otitis) will be assessed one a week by a study nurse | Starting from inclusion, weekly during a follow-up of 6 months | 
| Infant's intestinal permeability | Intestinal permeability will be assessed using a mannitol-lactulose test | at inclusion, 3 months and 6 months after inclusion | 
| Residual fecal microbiota range-weighted richness | Composition of fecal microbiota will be determined by Illumina sequencing, from which range-weighted richness will be calculated | 3 months and 6 months | 
| Residual concentration of short-chain fatty acids in stool | Concentration of short chain fatty acids (acetate, butyrate and propionate) will be measured by Gas Chromatography | 3 months and 6 months |