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

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.

Study Overview

• Status: Completed
• Conditions: Dysbiosis
• Intervention / Treatment: Dietary supplement: L. reuteri; Dietary supplement: B. longum and P. Pentosaceus

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Neonatal Unit, Hospital Clinic-Maternitat
  • Madrid, Spain, 28938
    • Fundación HM Hospitales (Hospital HM Puerta Sur)
  • Barcelona
    • Sant Cugat del Valles, Barcelona, Spain, 08195
      • Hospital Universitari General de Catalunya

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Healthy infants up to 25 days 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 feeding per day) or mixed feeding (in which there is more than one formula feeding 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative abundance of bifidobacteria	Changes in the relative abundance of bifidobacteria in stool microbiota after 1 month of supplementation, measured with metagenomic techniques.	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
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
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. Analysis will comprise changes in the relative abundance of B. longum and P. Pentosaceous as well as the order Bifidobacteriales, Lactobacillales , Bacteroidales and Enterobacterales. In addition, the proportion (Bifidobacteriales + Lactobacillales + Bacteroidales) will be determined	1 month

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2020
• Primary Completion (Actual): March 12, 2024
• Study Completion (Actual): November 30, 2024

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 15, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: probiotic; newborn; microbiota
• Additional Relevant MeSH Terms: Pathologic Processes; Dysbiosis; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents, Urinary; Sulfalene
• Other Study ID Numbers: Pro-Care 3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No