Microbiome and its impact on fetal and neonatal brain development: current opinion in pediatrics.

PURPOSE OF REVIEW: Emerging evidence suggests that the gut microbiota and its metabolites regulate neurodevelopment and cognitive functioning via a bi-directional communication system known as the microbiota-gut-brain axis (MGBA). RECENT FINDINGS: The MGBA influences brain development and function via the hypothalamic-pituitary axis, the vagal nerve, immune signaling, bacterial production of neurotransmitters, and microbial metabolites like short-chain fatty acids, tryptophan derivatives, and bile acids. Animal studies show fetal neurodevelopment is mediated by maternal microbiota derivatives, immune activation, and diet. Furthermore, manipulation of the microbiota during critical windows of development, like antibiotic exposure and fecal microbiota transplantation, can affect cognitive functioning and behavior in mice. Evidence from human studies, particularly in preterm infants, also suggests that a disrupted gut microbiota colonization may negatively affect neurodevelopment. Early microbial signatures were linked to favorable and adverse neurodevelopmental outcomes. SUMMARY: The link between the gut microbiota and the brain is evident. Future studies, including experimental studies, larger participant cohort studies with longitudinal analyses of microbes, their metabolites, and neurotransmitters, and randomized controlled trials are warranted to further elucidate the mechanisms of the MGBA. Identification of early, predictive microbial markers could pave the way for the development of novel early microbiota-based intervention strategies, such as targeted probiotics, and vaginal or fecal microbiota transplantation, aimed at improving infant neurodevelopment.

Fecal Volatile Metabolomics Predict Gram-Negative Late-Onset Sepsis in Preterm Infants: A Nationwide Case-Control Study.

Early detection of late-onset sepsis (LOS) in preterm infants is crucial since timely treatment initiation is a key prognostic factor. We hypothesized that fecal volatile organic compounds (VOCs), reflecting microbiota composition and function, could serve as a non-invasive biomarker for preclinical pathogen-specific LOS detection. Fecal samples and clinical data of all preterm infants (≤30 weeks' gestation) admitted at nine neonatal intensive care units in the Netherlands and Belgium were collected daily. Samples from one to three days before LOS onset were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS), a technique based on pattern recognition, and gas chromatography-time of flight-mass spectrometry (GC-TOF-MS), to identify unique metabolites. Fecal VOC profiles and metabolites from infants with LOS were compared with matched controls. Samples from 121 LOS infants and 121 matched controls were analyzed using GC-IMS, and from 34 LOS infants and 34 matched controls using GC-TOF-MS. Differences in fecal VOCs were most profound one and two days preceding Escherichia coli LOS (Area Under Curve; p-value: 0.73; p = 0.02, 0.83; p < 0.002, respectively) and two and three days before gram-negative LOS (0.81; p < 0.001, 0.85; p < 0.001, respectively). GC-TOF-MS identified pathogen-specific discriminative metabolites for LOS. This study underlines the potential for VOCs as a non-invasive preclinical diagnostic LOS biomarker.

Detection of spontaneous preterm birth by maternal urinary volatile organic compound analysis: A prospective cohort study.

Accurate prediction of preterm birth is currently challenging, resulting in unnecessary maternal hospital admittance and fetal overexposure to antenatal corticosteroids. Novel biomarkers like volatile organic compounds (VOCs) hold potential for predictive, bed-side clinical applicability. In a proof of principle study, we aimed to assess the predictive potential of urinary volatile organic compounds in the identification of pregnant women at risk for preterm birth. Urine samples of women with a high risk for preterm birth (≧24 + 0 until 36 + 6 weeks) were collected prospectively and analyzed for VOCs using gas chromatography coupled with an ion mobility spectrometer (GS-IMS). Urinary VOCs of women delivering preterm were compared with urine samples of women with suspicion of preterm birth collected at the same gestation period but delivering at term. Additionally, the results were also interpreted in combination with patient characteristics, such as physical examination at admission, microbial cultures, and placental pathology. In our cohort, we found that urinary VOCs of women admitted for imminent preterm birth were not significantly different in the overall group of women delivering preterm vs. term. However, urinary VOCs of women admitted for imminent preterm birth and delivering between 28 + 0 until 36 + 6 weeks compared to women with a high risk for preterm birth during the same gestation period and eventually delivering at term (>37 + 0 weeks) differed significantly (area under the curve: 0.70). In addition, based on the same urinary VOCs, we could identify women with a confirmed chorioamnionitis (area under the curve: 0.72) and urinary tract infection (area under the curve: 0.97). In conclusion, urinary VOCs hold potential for non-invasive, bedside prediction of preterm birth and on the spot identification of intra-uterine infection and urinary tract infections. We suggest these observations are further explored in larger populations.