Title : Early-life gut microbiome signatures associated with growth failure in infants with congenital heart defects
Abstract:
Background: Infants with Congenital Heart Defects (CHD) frequently experience growth failure and metabolic disturbances that cannot be fully explained by hemodynamic factors alone. Increasing evidence suggests that early-life gut microbiome dysbiosis may contribute to impaired nutrient utilization, inflammation, and adverse clinical outcomes.
Objective: To investigate gut microbiome signatures and their association with metabolic alterations, inflammation, and growth outcomes in neonates with CHD.
Methods: A cohort of 150 neonates with CHD and 50 healthy controls was studied using deep metagenomic sequencing and metabolomic profiling of paired fecal samples. Microbial composition, functional potential, and genetic variability were analyzed. The intestinal virome was characterized to assess viral–bacterial interactions. Anthropometric indices were evaluated using WHO Z-scores. Statistical analyses included multivariate regression, correlation analysis (Spearman’s ρ), and mediation modeling.
Results: Infants with CHD demonstrated significant gut microbiome dysbiosis, with a reduction in Bifidobacterium abundance (median relative abundance 12.4% vs. 28.7% in controls, p<0.001) and overgrowth of Enterococcus (18.9% vs. 6.3%, p<0.001). These alterations were associated with lower weight-for-age Z-scores (−1.9±0.6 vs. −0.8±0.4, p<0.01). Reduced Bifidobacterium levels correlated positively with short-chain fatty acid concentrations (ρ=0.62, p<0.001), whereas Enterococcus abundance showed a strong positive correlation with inflammatory markers (ρ=0.58, p<0.001). Genetic variability within these taxa was linked to altered metabolic pathways involved in carbohydrate fermentation and energy production. Virome analysis revealed a stable core dominated by Siphoviridae, contributing to microbial community restructuring through modulation of bacterial adaptation. In subgroup analysis, elevated Enterococcus abundance was associated with increased risk of adverse surgical outcomes (OR=2.8; 95% CI: 1.5-5.2; p=0.002). Mediation analysis indicated that Enterococcus overgrowth accounted for approximately 34% of the effect on intestinal barrier dysfunction and systemic inflammation.
Conclusion: Gut microbiome dysbiosis in early life, characterized by depletion of beneficial bacteria and expansion of opportunistic taxa, is strongly associated with metabolic impairment, inflammation, and growth failure in infants with CHD. These findings highlight the microbiome as a potential therapeutic target for improving clinical outcomes and supporting growth and immune homeostasis.
