{
  "abstract": "Background Late-onset sepsis (LOS) remains a leading cause of morbidity in preterm infants. While gut dysbiosis is a known risk factor, the specific temporal dynamics preceding sepsis are often confounded by clinical variables like delivery mode. This study aimed to identify pre-clinical microbiome signatures associated with LOS by characterizing longitudinal shifts in specific diversity metrics and taxa, rigorously differentiating true disease markers from confounders using multivariable models.Methods We conducted a nested longitudinal case-control study analyzing 106 fecal samples from 66 preterm infants (<37 weeks’ gestation; 14 LOS cases, 52 matched controls). Samples were collected at Week 1 and Week 2 of life, strictly prior to sepsis onset (median onset Day 39.5) ( IDDF2026-ABS-0040 Figure 1. Study timeline).16S rRNA gene sequencing was performed. We utilized Linear Mixed-Effects Models (LMM) to assess longitudinal dynamics of richness (Observed/Chao1) and multivariable linear modeling (MaAsLin2) to identify specific taxonomic associations, adjusting for delivery mode, antibiotic use, and repeated measures.Results At Week 1, the microbiome was comparable between groups. However, longitudinal modeling revealed a critical ‘ecological stagnation’ in infants progressing to sepsis. While controls significantly expanded microbial richness from Week 1 to Week 2 ( P<0.001), LOS infants showed no significant gain, resulting in significantly reduced Observed Features (P=0.016) and a significant Group-Time interaction (P=0.046) regarding richness (IDDF2026-ABS-0040 Figure 2. Ecological stagnation). Crucially, MaAsLin2 analysis disentangled confounders: the bloom of Escherichia was primarily driven by vaginal delivery (Coefficient=2.94, P=0.029) rather than sepsis (IDDF2026-ABS-0040 Figure 4. Confounder analysis). Conversely, Klebsiella was identified as a robust, independent disease signature, being significantly depleted in the sepsis group during the second week (Log2 Fold Change = -3.70, P=0.011) (IDDF2026-ABS-0040 Figure 3. Sepsis-specific depletion) and longitudinally (P=0.042).Conclusions LOS is preceded by a quantifiable arrest in gut microbiome maturation (stagnation of richness) during the second week of life. Furthermore, we distinguish Klebsiella depletion as a specific pre-sepsis marker, while Escherichia abundance largely reflects delivery mode. These findings suggest that monitoring ecological stagnation and non-invasive taxonomic signatures could facilitate early risk stratification for LOS.Abstract IDDF2026-ABS-0040 Figure 1Abstract IDDF2026-ABS-0040 Figure 2Abstract IDDF2026-ABS-0040 Figure 3Abstract IDDF2026-ABS-0040 Figure 4",
  "authors": [
    {
      "affiliations": [
        "The Chinese University of Hong Kong, Hong Kong"
      ],
      "name": "Xinxin Liu"
    },
    {
      "affiliations": [
        "The Chinese University of Hong Kong, Hong Kong"
      ],
      "name": "Hugh Simon Hung-San Lam"
    }
  ],
  "title": "IDDF2026-ABS-0040 Early gut microbiome stagnation and specific taxonomic signatures precede late-onset sepsis in preterm infants: a longitudinal case-control study",
  "uid": "81559bce-dab7-52ef-81d2-22827b16f9fc"
}