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The Premature Infants' Gut Microbiota Assembly and Neurodevelopment (PIGMAN) Cohort Study: Protocol for a
Tingting Li1, Liangfeng Fang1, Xianhong Chen2,3
1Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children's Hospital (Longgang) of Shantou University Medical College), Shenzhen 518172, China.
Background:
Early-life gut microbiota colonization plays a significant role in the neurodevelopment of infants and young children. However, the causal relationship between early-life gut microbiota colonization and neurodevelopment in preterm infants has not yet been conclusively established. Our research will initiate the PIGMAN (Premature Infants Gut Microbiota Assembly and Neurodevelopment) cohort study to systematically examine the dynamic interplay between gut microbiota developmental trajectories and neurodevelopmental processes in preterm infants.
Methods:
This study will employ a longitudinal cohort design and utilize data from the PIGMAN cohort, examining the interplay between gut microbiota metabolism and neurodevelopmental outcomes. The study design incorporates longitudinal stool sample collection, which will be analyzed through 16S rRNA gene sequencing and metagenomic shotgun sequencing, enabling comprehensive characterization of microbial community dynamics and functional metabolic pathways.
Anticipated Results:
Advanced analytical approaches incorporating causal inference methodologies will be implemented to identify significant microbial and metabolic biomarkers associated with neurodevelopmental outcomes in preterm neonates, and to establish causal pathways between these biomarkers and neurodevelopment. These analytical advancements will facilitate the construction of predictive models that utilize temporal microbial signatures and metabolite trajectories as prognostic indicators for neurodevelopmental outcomes. Causal inference method evaluations will further reveal that specific gut-derived metabolites, particularly those involved in cholesterol metabolism and neural signaling pathways-such as bile acids and GABA (gamma-aminobutyric acid)-exhibit superior predictive capacity for cognitive development trajectories. Anticipated Conclusions: The findings will collectively suggest that longitudinal metabolic profiling of the gut ecosystem, when combined with causal network analysis, provides a novel paradigm for developing clinically actionable predictive models of neurodevelopment in vulnerable preterm populations.
