Session: Neonatal Infectious Diseases/Immunology 4: Immunity in early life
062 - Bacterial extracellular vesicles (BEVs) from stool of preterm infants with and without antibiotic therapy modulate innate immune cells
Sunday, April 27, 2025
8:30am – 10:45am HST
Publication Number: 62.3956
till Lesk, University Hospital of Tübingen, Tübingen, Baden-Wurttemberg, Germany; Stefanie Dietz-Ziegler, Heidelberg University, Medical Faculty, Department of Neonatology, Heidelberg, Baden-Wurttemberg, Germany; Natascha Köstlin-Gille, University Hospital Tübingen, Tübingen, Baden-Wurttemberg, Germany; christian F. Poets, Tübingen University Hospital, Tuebingen, Baden-Wurttemberg, Germany; Christian Gille, Heidelberg University, Heidelberg, Baden-Wurttemberg, Germany
Student University Hospital of Tübingen Tübingen, Baden-Wurttemberg, Germany
Background: Bacterial infections are one of the most important causes of death in preterm infants. Approximately 20% of very low birth weight infants (VLBW; < 1500 g) develop a serious systemic bacterial infection during their stay in the neonatal intensive care unit. For this reason, up to 80% of preterm infants receive antibiotics within their first postnatal week. Early antibiotic treatment, however, is associated with an increased risk of infections in the neonatal period such as necrotizing enterocolitis (NEC). The intestinal microbiome contributes significantly to physiologic processes, but can also be involved in the development of diseases in case of pathological changes (dysbiosis). An important factor leading to dysregulation of microbiome establishment appears to be prenatal and early postnatal antibiotic exposure (EAE). One mechanism by which the intestinal microbiome communicates with the host is via extracellular vesicles (EVs) produced by intestinal bacteria. Objective: In our study, we investigated how BEVs from the stool of preterm infants influence innate immune responses and whether early antibiotic exposure modulates the effect of BEVs on immune cells. Design/Methods: As part of a clinical trial, we collected stool samples from preterm infants with and without EAE in their first week of life at postnatal day 14 and at a corrected age of four months. We isolated BEVs and investigated the effect of BEVs on monocytes in an in vitro co-culture model. Results: BEVs from stool of preterm infants with and without EAE did not differ in size, concentration or lipoteichoic acid and endotoxin content. Stimulation with BEVs from preterm infants induced production of cytokines TNF-α, IL-1ß, IL-6, Il-8, IL-4, IL-10, TGF-ß and IFN-γ by monocytes. With increasing postnatal age, there was an increased induction of proinflammatory cytokines and a decreased induction of anti-inflammatory cytokines by BEVs. BEVs from preterm infants with EAE led to a stronger induction of IL-1ß production by monocytes than BEVs from preterm infants without EAE.
Conclusion(s): BEVs from the stool of preterm infants have different effects on monocytes depending on infants’ age and EAE. Increased stimulation of the inflammasome effector cytokine IL-1β by BEVs from preterm infants with EAE could be a sign of increased activation of certain proinflammatory signaling pathways that may contribute to the increased risk of hyperinflammatory diseases such as NEC.
