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Fecal Microbiota and Volatile Metabolome Pattern Alterations Precede Late-Onset Meningitis in Preterm Neonates.
Nina M Frerichs1,2,3, Nancy Deianova1,2,3, Sofia El Manouni El Hassani1,2,3
1Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands.
The Journal of Infectious Diseases
|May 23, 2024
Summary
Altered gut microbiota can predict late-onset neonatal meningitis (LOM) in preterm infants up to three days before diagnosis. Fecal microbiota analysis offers a promising non-invasive method for early LOM detection.
Area of Science:
- Neonatal Medicine
- Microbiome Research
- Infectious Diseases
Background:
- Late-onset neonatal meningitis (LOM) shares similarities with late-onset sepsis (LOS), suggesting potential preclinical alterations in the gut microbiome and metabolome.
- Investigating these changes may lead to early detection and improved outcomes for preterm infants.
Purpose of the Study:
- To identify specific fecal microbiota compositions and volatile metabolomic profiles that precede the onset of LOM in preterm infants.
- To evaluate the predictive potential of these biomarkers for LOM development.
Main Methods:
- A prospective, longitudinal study of preterm infants (<30 weeks' gestation) from nine NICUs.
- Fecal samples were collected 1-10 days before LOM diagnosis and analyzed for microbial composition (16S rRNA sequencing) and volatile metabolome (GC-IMS, GC-TOF-MS).
- Machine learning models (Random Forest) and statistical analyses (MaAsLin2) were employed for data interpretation.
Main Results:
- A Random Forest model using six microbiota features accurately predicted LOM 1-3 days prior to diagnosis (AUC=0.88).
- Volatile metabolomics showed moderate predictive value (AUC=0.70-0.76) in the three days preceding LOM.
- No single metabolite was identified as a significant differentiator.
Conclusions:
- Preclinical fecal microbiota composition can accurately distinguish infants who will develop LOM from controls.
- Alterations in the volatile metabolome show a moderate association with preclinical LOM.
- Microbiota profiling holds promise for early, non-invasive LOM detection in high-risk infants.
