NapBiome: Targeting Gut Microbiota and Sleep Rhythm to Improve Developmental and Behavioral Outcomes in Early Childhood

Not Applicable

Not yet recruiting

• Conditions: Sleep Problem; Neurobehavioral Manifestations
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Synbiotic

• Registration Number: NCT06396689
• Lead Sponsor: Petra Zimmermann

Brief Summary

The gut-brain axis plays a crucial role in the regulation and development of psychological and physical processes. The first year of life is a critical period for the development of the gut microbiome, which parallels important milestones in establishing sleep rhythm and neurodevelopment. Growing evidence suggests that the gut microbiome influences sleep, cognition, and early neurodevelopment. For term and preterm-born infants, difficulties in sleep regulation can have major consequences on infants' health, attachment between infants and their caregivers, and can even lead to life-threatening consequences such as shaken-baby syndrome. Preterm born infants are at even higher risk for sleep and neurodevelopmental problems. Although neonatal care has improved over recent decades, preterm birth rates continue to rise and lead to a wide range of neurodevelopmental disabilities that are unaddressed with current therapies. Given the importance of sleep and the gut microbiome for brain maturation, neurodevelopment, and behavior, identifying effective interventions within the gut-brain axis at the beginning of life is likely to have long-term implications for health and development of at-risk infants.

The aims of this project are to I) demonstrate the association between the gut microbiome, sleep patterns and health outcomes in children up to two years of age; and II) to leverage gut microbiome-brain-sleep interactions to develop new intervention strategies for at-risk infants. The investigators hypothesize that the establishment of a healthy gut microbiome during early life is crucial for both short- and long-term child health outcomes, as dysbiosis can harm sleep regulation, brain maturation, and neurobehavioral development. The investigators predict that the administration of synbiotics improves microbiota establishment, sleep rhythm, and neurodevelopmental outcomes.

This project integrates a randomized controlled trial (RCT), ex vivo, and in silico experiments with I) key technology platforms for computational modeling to capture the ontogenic norms of gut microbiota; II) neuronal and actimetry-based quantification of multidimensional aspects of infant sleep; III) breath metabolomics (exhalomics) of host and microbiome metabolism; and IV) high-throughput ex vivo models for investigating host-microbiome interactions. Outcomes include I) an understanding of age-normative microbiome composition, its variation (circadian, inter-individual), and the factors that influence the microbiome's plasticity throughout infancy; II) actionable knowledge of microbial species and metabolism that can be targeted to modify sleep regulation and improve neurodevelopmental outcomes, especially in at-risk infants (e.g., preterm-born); III) microbial and metabolic biomarkers with diagnostic potential for later regulatory and behavioral problems; and IV) an open-source analytical "toolbox" for microbial multi-omics that can be immediately applied in other areas of microbiome-host research. To achieve these goals, our strategy combines multiple disciplines focusing on factors that exert the greatest influence on health during infancy: the gut microbiome, sleep regulation, and neurodevelopment.

The impact of this project is substantial and globally relevant, as it advances possible treatment options for supporting neurodevelopmental health in preterm- and term-born infants, explores novel translational approaches for addressing regulatory difficulties, and provides key information for tailored prophylactic synbiotics and possible development of "post-biotics". Further, the study supports the investigation of biomarkers for neurodevelopment and advances early prevention of developmental and mental illnesses.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-10
• Study First Submitted QC: 2024-04-29
• Study First Posted: 2024-05-02
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-20
• Study Start: 2025-03-01
• Primary Completion: 2029-02-28
• Study Completion: 2029-02-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

Preterm-arm:

• neonates born between a gestational age of 34 0/7 to 36 6/7 weeks
• partially breast-fed at the time of inclusion

Term-arm

• neonates born at a gestational age of ≥ 37 0/7 weeks Infants need to be
• partially breast-fed at the time of inclusion

Exclusion Criteria

Infants who

• receive probiotics outside the trial design
• have a birth weight < 1500 g
• were prenatally drug-exposed (cannabis, cocaine, heroin, opiates, and alcohol)
• have suspected or confirmed immunodeficiency
• have an underlying disease (excluding transient conditions such as alimentation problems, hyperbilirubinemia, hypoglycaemia, anemia, respiratory distress syndrome or apnea-bradycardia syndrome), congenital malformations, central nervous system disease or injury or congenital infections

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Term-born infants to "placebo" (TER-PLC)	Placebo	-
Term-born infants to "synbiotics" (TER-SYN)	Synbiotic	-
Preterm-born infants to "placebo" (PRE-PLC)	Placebo	-
Preterm-born infants assigned to "synbiotics" (PRE-SYN)	Synbiotic	-

Primary Outcome Measures

Name	Time	Method
Sleep-wake behavior	up to two years of age	Brief Infant Sleep Questionnaire BISQ, actinometry and sleep-wake diary
Neuronal connectivity	up to two years of age	High-density EEG during sleep
Neurobehavioral development	up to two years of age	Bayley Scales of Infant Development
Behavior	up to two years of age	Infant Behavior Questionnaire
Gut microbiota	up to two years of age	Composition of stool microbiota
Stool metabolome	up to two years of age	Composition of stool metabolites
Breath metabolome	up to two years of age	Composition of breath metabolites

Secondary Outcome Measures

Name	Time	Method
Oral microbiota	up to two years of age	Composition investigated trough shotgun metagenomic sequencing
Eczema	up to two years of age	SCORing Atopic Dermatitis scoring system (SCORAD)
Nasal microbiota	up to two years of age	Composition investigated trough shotgun metagenomic sequencing
Food allergy	up to two years of age	Skin prick test
Rates of infection	up to two years of age	Number of episodes
Breast milk microbiota	up to two years of age	Composition investigated trough shotgun metagenomic sequencing

Trial Locations

Locations (2)

Cantonal Hospital; 🇨🇭 Lucerne, Switzerland

Hopital cantonal Fribourg; 🇨🇭 Fribourg, Switzerland