Effects of prenatal bifidobacterium supplementation on the gut microbiome in preterm infants of preeclamptic mothers.

backgroundThis study examined the relationship between maternal preeclampsia (PE) and gut microbiota colonization in preterm infants and analyzed the effects of prenatal Bifidobacterium supplementation.

methodsThis observational study included 45 preterm infants categorized according to their mothers' exposure status during pregnancy. Group A (healthy controls, n = 15) included infants born to healthy mothers who received no supplementation; Group B (PE+Bifidobacterium, n = 15) included infants whose mothers had PE and received Bifidobacterium supplementation as part of routine clinical management; and Group C (PE only, n = 15) included infants born to mothers with PE who did not receive Bifidobacterium supplementation. All enrolled infants were followed from birth for subsequent analyses. The initial postnatal fecal samples of the infants were collected and analyzed using 16S rRNA gene sequencing. Microbial diversity within the intestinal microbiota was evaluated using alpha diversity (within-sample) and beta diversity (between-sample) analyses. To identify taxon-specific differences among groups, we performed linear discriminant analysis effect size and differential abundance analysis, with statistical significance set at p < 0.05. The functional potential of the gut microbiota was inferred based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways via the PICRUSt2 algorithm.

resultsAlpha diversity analysis revealed significantly greater microbial diversity in the fecal microbiota of preterm infants born to healthy mothers (Group A) than in those delivered by mothers with PE, regardless of prenatal Bifidobacterium exposure. Taxonomic profiling revealed distinct microbial community structures across groups: Group A exhibited significant enrichment of Bacteroides at all taxonomic levels, along with an elevated abundance of Clostridium at the class and order levels. Group B showed a markedly greater relative abundance of Actinobacteria at the phylum level and Rothia at the genus level, whereas Group C was dominated by Proteobacteria (phylum level) and Streptococcus (genus level). All intergroup differences were statistically significant following Benjamini‒Hochberg correction (q < 0.05). A functional analysis of the gut microbiota revealed 53 KEGG pathways with significant overall group differences (p < 0.05), among which 23 pathways were significantly different in at least two groups (q < 0.05). Notably, the activity of the LPS biosynthesis pathway was significantly upregulated in Group C compared with Group A (q = 0.001). Although LPS biosynthesis activity was reduced in Group B relative to Group C (q = 0.018), it remained elevated compared to Group A (q = 0.001), suggesting incomplete mitigation of endotoxin risk. Additionally, glycolytic activity was significantly impaired in Group C relative to Group A (q = 0.003) but was partially restored in Group B compared to Group C (q = 0.022).

conclusionsMaternal PE impaired early-life gut microbiota establishment in preterm infants, manifesting in reduced microbial diversity, enrichment of pathogenic Proteobacteria and Streptococcus, and consequent functional dysbiosis characterized by elevated endotoxin biosynthesis potential and compromised energy metabolism. Although prenatal supplementation with Bifidobacterium partially restored the microbial compositional balance, promoting beneficial bacteria, reducing LPS synthesis activity, and partially improving glycolytic function, it failed to fully reverse endotoxin-related risks, indicating the need to develop more effective microbiota-targeted strategies to comprehensively optimize metabolic and immune homeostasis.