article · bioRxiv (Cold Spring Harbor Laboratory)
ABSTRACT Background Chronic malnutrition in early childhood is a multifactorial condition associated with long-term impairments, yet the physiological and gut microbial pathways underlying differential growth trajectories remain poorly understood. Objective We aimed to characterize phenotypic growth trajectories and identify the associated gut microbial and body composition signatures in infants during the first year of life. Methods We analyzed longitudinal data from birth to 12 months in a South African cohort (Soweto, n=45). Individual linear growth trajectories were modeled using the Jenss-Bayley equation, and children were clustered based on model parameters to identify phenotypic subgroups. Body composition (fat-free mass and fat mass) was measured via deuterium dilution at 6 and 12 months, and gut microbiome development was assessed using 16S rRNA gene amplicons at 4, 6, and 12 months. Results We identified distinct phenotypic subgroups including healthy growth, catch-up growth, and growth faltering, that were obscured at the cohort level. These trajectories diverged most dynamically within the first 6 months of life. Integrated analysis revealed that in the growth faltering cluster, height-for-age and fat-free mass z-scores stabilized between 6 and 12 months, whereas fat mass z-scores (FMZ) declined. This trade-off is consistent with a catabolic state where energy reserves are prioritized for lean tissue and bone growth. Furthermore, at 6 months, the growth faltering cluster was enriched with opportunistic pathobionts (e.g., Paraclostridium ). In contrast, the catch-up cluster exhibited a transient enrichment of facultative anaerobes (e.g., Enterobacter ), supporting a hypothesis that these oxygen-tolerant taxa may help bridge a transitional microbial state in partially oxygenated or inflamed environments to enable physiological recovery. Conclusions Early childhood chronic malnutrition phenotypes in South African infants can be defined by distinct microbial and body composition signatures that diverge within six months of life. Integrated interventions should target both host anabolic state and microbiome transitions to support recovery.
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DOI: 10.64898/2026.05.11.723332
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