226 - Inhalation of Lacticaseibacillus Rhamnosus Prevents Severe Bronchopulmonary Dysplasia in Mice

Publication Number: 226.5388

Jessica D.. Ruehle, Heidelberg University, Medical Faculty, Department of Neonatology, Heidelberg, Baden-Wurttemberg, Germany; Stefanie Dietz-Ziegler, Heidelberg University, Medical Faculty, Department of Neonatology, Heidelberg, Baden-Wurttemberg, Germany; Janine Hebel, Childrens University Hospital Tübingen, Tuebingen, Baden-Wurttemberg, Germany; christian F. Poets, Tübingen University Hospital, Tuebingen, Baden-Wurttemberg, Germany; Christian Gille, Heidelberg University, Heidelberg, Baden-Wurttemberg, Germany; Natascha Köstlin-Gille, University Hospital Tübingen, Tübingen, Baden-Wurttemberg, Germany

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications in extremely preterm infants. In addition to mechanical lung damage and oxygen toxicity, inflammation plays a significant role in its pathogenesis.
The microbiome plays a pivotal role in maintaining health and in the pathogenesis of disease. In recent years, different studies have shown that the lungs of healthy individuals harbor a microbiome and that colonization of the lungs of newborns is important for the maturation of airway immunity. However, little is known about whether the airway microbiome plays a role in the pathogenesis of BPD.

Objective: In this study we aimed to investigate the hypotheses that inhalation of Lacticaseibacillus rhamnosus alters the airway microbiome, impacts the maturation of airway immunity and has a protective effect on a BPD model in mice.

Design/Methods: We administered L. rhamnosus (LR) daily via inhalation to newborn mice starting from postnatal day 1 (P1) until weaning or until the end of the experiment. Airway microbiome and airway immune cell composition were analyzed at different timepoints by qPCR, 16s rRNA sequencing and flow cytometry.
BPD was experimentally induced in newborn mice by hyperoxia for seven days and intraperitoneal injection of LPS at postnatal day 3. One part of the animals was inhaled with L. rhamnosus once daily from P1 onwards. On P8 and P21, animals were euthanized, and lungs were histologically examined for signs of BPD.

Results: Inhalation of L. rhamnosus was accompanied by an increase in Firmicutes in the airway microbiome as assessed by qPCR. 16s rRNA sequencing analyses are still pending at the time of abstract submission. Furthermore, we observed a reduced infiltration of myeloid cells into the lungs after inhalation, but an increased infiltration of B cells.
Inhalation of L. rhamnosus reduced the severity of the BPD as shown by reduced alveolar size and restored the histological phenotype of healthy mice. Analysis of the immune cell populations showed again that in the lung, inhalation resulted in a reduced influx of myeloid cells and an increased influx of B cells in our BPD model compared to systemic immune cells in the spleen.

Conclusion(s): The current results suggest beneficial effects of L. rhamnosus inhalation for BPD prevention. Further analyses are necessary to decipher the exact mechanisms underlying this favorable effect and to analyze potential systemic side effects.