Effects of early-life gut microbiota on the neurodevelopmental outcomes of preterm infants: a multi-center, longitudinal observational study in China.

ABSTRACT

To prospectively investigate associations between the features of gut microbiota at the fourth week after birth in preterm infants and neurodevelopment from 1 month of corrected age to 6 months of corrected age (MCA). Seventy-seven preterm infants were recruited from three NICUs of three tertiary hospitals between Apr 2021 to Sep 2022. Stool samples were collected during the fourth week after birth. Illumina MiSeq high-throughput sequencing technology was used to detect the composition and diversity of gut microbiota. Neurodevelopment assessments of preterm infants were conducted at 1, 3, and 6 MCA using the Ages and Stages Questionnaire, the third edition (ASQ-3). Spearman correlation, a generalized linear mixed model (GLMM), and permutational multivariate analysis of variance (PERMANOVA) analysis were used to horizontally and prospectively explore the associations between gut microbial and ASQ-3 dimension scores at each time point. The GLMM showed no significant associations between the alpha diversity and neurodevelopmental trajectory from 1 to 6 MCA. The beta diversity was significantly associated with gross motor scores at 1, 3, and 6 MCA (R2 = 0.067, p = 0.001; R2 = 0.039, p = 0.020; R2 = 0.031, p = 0.047); communication scores at 3 MCA (R2 = 0.030, p = 0.040); and fine motor scores at 6 MCA (R2 = 0.035, p = 0.022). After adjusting for covariates, the GLMM showed that the relative abundance of Klebsiella was negatively associated with gross motor score trajectory from 1 to 6 MCA (ß = - 1.449; 95% CI, - 2.275 to - 0.572; p = 0.001), while the relative abundance of Lactobacillus displayed a positive association (ß = 1.421; 95% CI, 0.139 to 2.702; p = 0.030). Moreover, the relative abundance of Streptococcus was negatively associated with fine motor trajectory from 1 to 6 MCA (ß = - 1.669; 95% CI, - 3.305 to - 0.033; p = 0.046). CONCLUSION: Our results suggest a possible association between the neonatal gut microbial diversity; the relative abundance of Klebsiella, Streptococcus, and Lactobacillus; and neurodevelopment from 1 to 6 MCA. In the future, clinical staff can focus on the window period of gut microbiota colonization, and implement probiotics targeted at the dominant genera to improve the neurodevelopment of preterm infants. WHAT IS KNOWN • In the fields of biology and medicine, current studies suggest that gut microbiota may play an important role in the critical window period of neurodevelopment through the gut-brain axis pathway. • Extensive preclinical research has implied the vital role of the initial gut colonization in the long-term neurodevelopment of children. WHAT IS NEW • The early-life gut microbiota was associated with neurodevelopment in preterm infants within 6 months of corrected age (MCA).