AGE-DEPENDENT DISRUPTION OF GUT MICROBIOME MATURATION IN INFANTS AND YOUNG CHILDREN WITH CONGENITAL HEART DISEASE: A WHOLE-GENOME SHOTGUN METAGENOMIC SEQUENCING STUDY

Abstract

Congenital heart disease (CHD) may disturb intestinal perfusion, feeding, and early microbial succession, yet age resolved microbiome data from Central Asian children remain limited. We compared fecal bacterial communities in 73 children with CHD and 36 age-matched healthy controls aged 0-3 years. Participants were stratified into 0 6 months (CHD, n=18; control, n=12), 6-12 months (CHD, n=24; control, n=12), and 1-3 years (CHD, n=31; control, n=12). Bacterial community structure was characterized by whole-genome shotgun metagenomic sequencing. Alpha diversity, phylum-level composition, genus-level relative abundance, and the Firmicutes/Bacteroidota ratio were evaluated. Across all age strata, CHD was associated with reduced microbial richness and evenness. In infants aged 0-6 months, Shannon diversity was 1.49±0.09 in CHD versus 2.27±0.24 in controls, Pielou evenness was 0.52±0.02 versus 0.63±0.04, and the mean number of detected genera was 20.5±2.6 versus 40.4±5.9 (p<0.05). The divergence persisted at 1-3 years, when Shannon diversity was 2.22±0.07 versus 2.87±0.09 and Pielou evenness was 0.513±0.016 versus 0.69±0.03. CHD samples showed persistent enrichment of Proteobacteria and depletion of age-associated saccharolytic and butyrate-producing taxa. During the first 6 months, Escherichia/Shigella (21.7±6.9%), Enterococcus (10.5±4.0%), Enterobacter (9.2±3.0%), and Veillonella (12.8±2.0%) were increased, whereas Bifidobacterium (18.1±3.9% vs 50.4±11.2%) and Faecalibacterium (0.021±0.004% vs 1.02±0.04%) were reduced. Older children with CHD remained deficient in Agathobacter, Faecalibacterium, Roseburia, Lachnospira, and Subdoligranulum. These findings indicate delayed and incomplete microbiome maturation in young children with CHD, characterized by reduced ecological stability, expansion of facultative anaerobes, and loss of short-chain-fatty-acid-producing capacity. Longitudinal studies integrating feeding, medication exposure, cardiac phenotype, and metabolomics are warranted.