Effect of Probiotics on Infant's Fecal Microbiota Composition

Study Overview
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Brief Summary
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Randomized clinical trial to evaluate the effect of two probiotic strains which belong to Bifidobacterium Longum and Pediococcus pentosaceus species on fecal microbiota composition in healthy infants. Secondary outcomes comprise evaluation of anthropometric growth, digestive tolerance, sleeping habits, incidence of functional gastrointestinal disorders, incidence of gastrointestinal and respiratory infections, allergic reactions and safety and tolerability of the product.

Detailed Description
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Double-blind, randomized, placebo-controlled clinical trial to determine the effect of the probiotic strains Bifidobacterium longum and Pediococcus pentosaceus on fecal microbiota composition in infants. Healthy babies with ages comprised between 60 and 90 days who meet inclusion and exclusion criteria will be randomized 1:1:1 to one of the following study groups: one group will receive Bifidobacterium longum, another group will receive Pediococcus pentosaceus and the other one will receive placebo for 3 months. Other study outcomes comprise anthropometric growth, frequency and consistency of the stools, digestive tolerance, wellbeing, number, type and duration of infections and functional gastrointestinal disorders, and adverse events.

Official Title
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Safety, Tolerability and Effect on Fecal Microbiota Composition of Two Probiotic Strains in Infants

Conditions
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Microbial Colonization

Intervention / Treatment
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* Dietary Supplement: Food Supplement 1
* Dietary Supplement: Food Supplement 2
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants Age between 60 and 90 days Gestational age between 37 and 42 weeks Appropiate birth weight for gestational age (between P10 and P90) APGAR test score for birth normal at 1' and 5' of 7-10 Whose parents accept the follow-up of the study procedures and sign the informed consent Exclusion Criteria: Infants participating in other clinical study Fed with infant formula containing probiotics or other aliments or food supplement based in probiotics 4 weeks prior the start of the study Infants who have taken antibiotics 4 weeks prior the start study Infants with cow's milk protein allergy, lactose intolerance or other digestive diseases Mother's pathological background and during gestation: neurologic disorders, matabolopaties, diabetes mellitus type 1, chronic disease (hypothyroidism), maternal malnutrition Acute congenital or acquired diseases which can interfere with the growth and the normal feeding of the infant TORCH complex infections Every other diseases related with the immune system Parents who can not accomplish the follow-up of the study (medical criterium)

Ages Eligible for Study
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Minimum Age: 60 Days
Maximum Age: 90 Days

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized, placebo-controlled trial in 120 healthy infants between 60 and 90 days of age, who will be allocated to receive either one of the probiotic strains or placebo for 3 months
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 1<br>Probiotic single strain formulation comprising Bifidobacterium longum CECT7894 in liquid format suspended in sunflower oil. This probiotic strain has Qualified Presumption of Safety (QPS) status by European Food Safety Authority. | Dietary Supplement: Food Supplement 1<br>* Probiotic single strain formulation containing Bifidobacterium longum CECT7894 for 3 months 5 drops/day<br>|
| Experimental: Experimental 2<br>Probiotic single strain formulation comprising Pediococcus pentosaceus CECT8330 in liquid format suspended in sunflower oil. This probiotic strain has Qualified Presumption of Safety (QPS) status by European Food Safety Authority. | Dietary Supplement: Food Supplement 2<br>* Probiotic single strain formulation containing Pediococcus pentosaceus CECT8330 for 3 months 5 drops/day<br>|
| Placebo Comparator: Placebo<br>Sunflower oil | Dietary Supplement: Placebo<br>* 5 drops/day for 3 months of sunflower oil<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Bifidobacterium longum and Pediococcus pentosaceus in feces | Change of total counts of Bifidobacterium longum and Pediococcus pentosaceus in feces determined by qPCR | day 0, month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight change | Change in weight (g per day) between day 0 and month 3 | day 0, month 1, month 2, month 3 | 
| Length change | Change in length (cm) between day 0 and month 3 | day 0, month 1, month 2, month 3 | 
| Head circumference change | Change in head circumference (cm) between day 0 and month 3 | day 0, month 1, month 2, month 3 | 
| BMI change | Change in BMI (kg/m2) between day 0 and month 3 | day 0, month 1, month 2, month 3 | 
| Frequency of depositions | Frequency of depositions (number stools/day) documented in participants diary | day 0, month 1, month 2, month 3 | 
| Consistency of stools | Consistency of stools through a 5-item scale: 1= hard balls, 2=hard-formed, 3=soft-formed, 4=half liquid and 5=liquid | day 0, month 1, month 2, month 3 | 
| Infant colic | Incidence of infant colic, defined as prolonged and recurrent periods of crying, agitation, or irritability without apparent cause that cannot be prevented or resolved by your caregivers, for three or more hours daily for three or more days a week | day 0, month 1, month 2, month 3 | 
| Vomiting | Incidence of vomiting (n/day) | day 0, month 1, month 2, month 3 | 
| Sleeping habits | Nocturnal sleeping (min/day), total sleeping hours (min/day) | day 0, month 1, month 2, month 3 | 
| Incidence of infections | Number and duration (in days) of any type of infectious episodes | day 0, month 1, month 2, month 3 | 
| Fever | Number of days with fever (axial body temperature higher than 37.5 ºC) | day 0, month 1, month 2, month 3 | 
| Antibiotics | Number of days with antibiotic treatment | day 0, month 1, month 2, month 3 | 
| Change in fecal microbiota composition | Analysis of α y β biodiversity, relative abundance of bacteria determined by 16S sequencing | day 0, month 3 | 
| sIgA in stool samples | Analysis of secretory Immunoglobulin A (sIgA) in stools through ELISA | day 0, month 3 | 
| Calprotectin | Analysis of fecal calprotectin through ELISA | day 0, month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Infants, Microbiota