Enteral Probiotics Alter Inflammatory Signaling and Lung Remodeling in a Neonatal Sepsis–Associated Lung Injury Model
Presenter Status
Fellow
Abstract Type
Basic Research
Primary Mentor or Principal Investigator
Venkatesh Sampath, MBBS, MRCPCH
Presentation Type
Poster
Start Date
21-5-2026 12:00 PM
End Date
21-5-2026 1:00 PM
Abstract Text
Background: In premature infants, sepsis-induced acute lung injury (ALI) is a known risk factor for the development of bronchopulmonary dysplasia (BPD), a chronic lung disease marked by impaired alveolar and vascular growth. The gut-lung axis, linking intestinal microbiota to pulmonary immune homeostasis, has emerged as a potential target to mitigate systemic inflammation. Data suggest probiotics reduce late-onset sepsis and necrotizing enterocolitis in premature neonates; however, their impact on pulmonary inflammation modulation remains uncertain. We hypothesized that enteral probiotics would attenuate Toll-like receptor (TLR)-induced inflammation and tissue remodeling in a murine model of neonatal sepsis-associated ALI and BPD.
Objectives/Goal: To determine whether early, multi-strain probiotic exposure attenuates systemic endotoxin lipopolysaccharide (LPS)-induced a) pro-inflammatory TLR signaling and ALI, and b) subsequent chronic alveolar remodeling in a murine model of neonatal sepsis-associated lung injury.
Methods/Design: C57BL6/J pups received enteral UltraFlora® Baby Probiotic (0.05 mL of 10⁸ CFU/mL) or vehicle. For the acute group, mice received probiotic or vehicle on postnatal days (P) 4–6, followed by intraperitoneal LPS (2 mg/kg) or saline at P6, then euthanized on P7. Lung samples underwent RT-PCR for inflammatory (Kc, Il-6, Il-1β) cytokine expression, as well as western blot analysis to evaluate lung p-p65 (NF-κB component), p-p38 (MAPK), ICAM1, iNOS, and cleaved caspase-3 (apoptosis) protein expression. In a separate BPD-model group, probiotic or vehicle was administered to mice on P4-7, and P10, followed by LPS or saline on P5 and P7, then euthanized on P14. Inflation-fixed P14 lungs were analyzed for alveolar remodeling using radial alveolar counts (RAC). ANOVA with Bonferroni corrections were performed for statistical analysis.
Results: With acute LPS exposure, probiotics appeared to exaggerate LPS-induced lung Il-1β and Kc expression, with Il-6 significantly increased. Despite elevated transcript levels, western blot revealed reduced phosphorylation of NF-κB (p65) and p38 MAPK with probiotic exposure as well as reduced iNOS and ICAM-1, suggesting suppression of pro-inflammatory TLR4 signaling. In the chronic model, probiotic treatment rescued LPS induced chronic alveolar remodeling as measured by higher RAC values.
Conclusions: Acute findings showed divergent transcriptional and post-translational responses to probiotic exposure, whereas the chronic model demonstrated partial recovery. Further investigation into the complex relationships between probiotics and sepsis-induced ALI is warranted.
Enteral Probiotics Alter Inflammatory Signaling and Lung Remodeling in a Neonatal Sepsis–Associated Lung Injury Model
Background: In premature infants, sepsis-induced acute lung injury (ALI) is a known risk factor for the development of bronchopulmonary dysplasia (BPD), a chronic lung disease marked by impaired alveolar and vascular growth. The gut-lung axis, linking intestinal microbiota to pulmonary immune homeostasis, has emerged as a potential target to mitigate systemic inflammation. Data suggest probiotics reduce late-onset sepsis and necrotizing enterocolitis in premature neonates; however, their impact on pulmonary inflammation modulation remains uncertain. We hypothesized that enteral probiotics would attenuate Toll-like receptor (TLR)-induced inflammation and tissue remodeling in a murine model of neonatal sepsis-associated ALI and BPD.
Objectives/Goal: To determine whether early, multi-strain probiotic exposure attenuates systemic endotoxin lipopolysaccharide (LPS)-induced a) pro-inflammatory TLR signaling and ALI, and b) subsequent chronic alveolar remodeling in a murine model of neonatal sepsis-associated lung injury.
Methods/Design: C57BL6/J pups received enteral UltraFlora® Baby Probiotic (0.05 mL of 10⁸ CFU/mL) or vehicle. For the acute group, mice received probiotic or vehicle on postnatal days (P) 4–6, followed by intraperitoneal LPS (2 mg/kg) or saline at P6, then euthanized on P7. Lung samples underwent RT-PCR for inflammatory (Kc, Il-6, Il-1β) cytokine expression, as well as western blot analysis to evaluate lung p-p65 (NF-κB component), p-p38 (MAPK), ICAM1, iNOS, and cleaved caspase-3 (apoptosis) protein expression. In a separate BPD-model group, probiotic or vehicle was administered to mice on P4-7, and P10, followed by LPS or saline on P5 and P7, then euthanized on P14. Inflation-fixed P14 lungs were analyzed for alveolar remodeling using radial alveolar counts (RAC). ANOVA with Bonferroni corrections were performed for statistical analysis.
Results: With acute LPS exposure, probiotics appeared to exaggerate LPS-induced lung Il-1β and Kc expression, with Il-6 significantly increased. Despite elevated transcript levels, western blot revealed reduced phosphorylation of NF-κB (p65) and p38 MAPK with probiotic exposure as well as reduced iNOS and ICAM-1, suggesting suppression of pro-inflammatory TLR4 signaling. In the chronic model, probiotic treatment rescued LPS induced chronic alveolar remodeling as measured by higher RAC values.
Conclusions: Acute findings showed divergent transcriptional and post-translational responses to probiotic exposure, whereas the chronic model demonstrated partial recovery. Further investigation into the complex relationships between probiotics and sepsis-induced ALI is warranted.
Comments
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Poster Board Number: 40