Assessment of the Impact of Type of Probiotic, Delivery Type and Feeding Type on Baby's Microbiota After Dysbiotic Delivery

Study Overview
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Brief Summary
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This study aims to determine the effect of three factors (delivery type, feeding type and the use of two different dietary supplements) on rebiosis after disbiotic delivery. This is a randomized, single-blinded study with two parallel arms. Group 1 will receive L. reuteri (10^8 CFU) once a day, group 2 will receive B. longum and P. Pentosaceus (10^9 CFU) once a day.

Detailed Description
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Gut colonization during the first days of life represents the start of the infant's own microbiota. This process is influenced by different factors: delivery type, feeding type, antibiotic treatment, etc. On the one hand, vaginally delivered babies are in contact with mother's vaginal and faecal microbiota. This fact will drive a neonatal gut colonization composed of vagina-associated bacteria. In contrast, babies born by C-section are more susceptible to be colonized by microorganisms present in the mother's skin. On the other hand, antibiotic administration during vaginal delivery also produces alterations in the vaginal microbiota of the mother. Described scenarios have been correlated to immunological and metabolic diseases such as asthma, allergies, diabetes or obesity. Moreover, disbiosis has also been associated to functional gastrointestinal disorders (FGID) in babies such as infant colic and functional constipation. After a disbiotic delivery, medical doctors usually recommend the use of probiotics to prevent rebiosis. Since the probiotics. L. reuteri, and B. longum and P. Pentosaceus have shown efficacy on FGID amelioration in previously published articles, these two probiotics were selected for the present study. All together, this study aims to characterize the role of three different parameters: type of probiotic, delivery type and feeding type.

Official Title
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Assessment of the Impact of Type of Probiotic, Delivery Type and Feeding Type on Baby's Microbiota After Dysbiotic Delivery

Conditions
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Dysbiosis

Intervention / Treatment
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* Dietary Supplement: L. reuteri
* Dietary Supplement: B. longum and P. Pentosaceus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants in their first week of life Infants with adequate weight according to the gestational age. Infants born by vaginal delivery whose mother was given antimicrobial prophylaxis or infants born by C-section. Gestational birth equal or greater than 37 weeks. Exclusive or almost exclusive breastfeeding - understanding almost exclusive the one in which there is a maximum of one formula dose per day - or mixt breastfeeding, the one in which there are more than one formula dose per day. Exclusion Criteria: Infants with smoker mother during pregnancy and after delivery. Infants whose parents cannot follow the study requirements Infants who have suffered neonatal admission or have suffered or suffer necrotizing enterocolitis, infectious disease, congenital malformation, short bowel syndrome or any serious illness. Infants who have taken probiotics before the start of the trial or who take formula with probiotics. Breast-fed infants whose mothers have taken probiotics within the two weeks before study inclusion. Infants who ingest special formulas as extensively hydrolysed formulas. Breast-fed infants whose mothers have excluded dairy products and egg products in their diet during breastfeeding Infants who take specific medication for the treatment of functional digestive disorders: antacids (type IBP or H2 blockers), laxatives (PEG, lactulose, magnesia), lactase and simethicone at the time of inclusion. Infants undergoing therapies with acupuncture, homeopathy, medicinal herbs, anti-inflammatories and antispasmodics at the time of inclusion.

Ages Eligible for Study
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Maximum Age: 1 Week

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L. reuteri<br>Group that will receive L. reuteri one dose per day in an oral suspension Intervention: Dietary Supplement: L. reuteri | Dietary Supplement: L. reuteri<br>* (10^8 CFU) once a day<br>|
| Experimental: B. longum and P. Pentosaceus<br>Group that will receive B. longum and P. Pentosaceus one dose per day in an oral suspension. Intervention: Dietary Supplement: B. longum and P. Pentosaceus | Dietary Supplement: B. longum and P. Pentosaceus<br>* (10^9 CFU) once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metagenomic analysis of gut microbiota | The achievement of a microbiota dominated by Bacteroides, Lactobacillus and Bifidobacterium, along with a decrease in Enterobacteria after 4 weeks of probiotic treatment. Faecal sampleswill be collected at baseline and 1 month after probiotic treatment. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of regurgitations by questionnaire included in patients' diary | Number of regurgitations will be documented by the parents each week for 3 months in patients diary | 3 months | 
| Number of constipation episodes by questionnaire included in patients' diary | Number of constipation episodes will be documented by the parents each week for 3 months in patients' diary | 3 months | 
| Number of infant colic episodes by questionnaire included in patients' diary | Number of constipation episodes will be documented by the parents each week for 3 months in patient's diary | 3 months | 
| Metagenomic analysis of total gut microbiota | This measure includes all bacteria detected in feaces by metagenomic analysis. Faecal samples will be collected at baseline and 1 month after probiotic treatment. | 1 month | 
| Respiratory, gastrointestinal infections and use of medication by questionnaire included in patients' diary | Number of respiratory, gastrointestinal infections and use of medication episodes will be documented by the parents each week for 3 months in patient's diary | 3 months | 
| Anxiety and depression by the validated Hospital Anxiety and Depression scale (HADS) | Anxiety and depression levels of the father and mother will be evaluated at baseline and 3 months after probiotic treatment through the Hospital Anxiety and Depression Scale (HADS) questionnaire will be. Odd questions (assess anxiety). Even questions (assess depression). Score less than or equal to 7 = no case. 8-10 = doubtful case Score equal to or greater than 11 = case | 3 months | 
| Extra visits to paediatrician/emergency by questionnaire included in the patient's diary | Number of paediatric visits and / or emergency access will be documented each week in the patient's diary during the 3 months of treatment | 3 months | 
| Number of Participants With Treatment-Related Adverse Events | Adverse events will be documented weekly in the patient's diary during the 3 months of treatment. | 3 months | 
| Levels of IgA in faeces | changes in IgA in faeces from baseline to 1 month of treatment | 1 month | 
| Weight evolution by the paedatrician in study visits | Changes on baby's body weight from baseline to 3 months of probiotic treatment | 3 months |