Advisor(s)
Michael Gray
Casey Weaver
Committee Member(s)
Charles Elson
Namasivyam Ambalavanan
Rakesh Patel
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Microbiology
Date of Award
9-11-2025
Abstract
Neonatal infection remains a leading cause of both neonatal morbidity and mortality worldwide, particularly in preterm infants. Probiotic bacteria have been demonstrated to protect against the development of neonatal intestinal dysbiosis, however, formulations and efficacy vary substantially, highlighting a critical gap in the current understanding of the mechanisms governing probiotic efficacy in this population. This gap is exacerbated by regulatory standards which favor economic expansion over scientific rigor. Furthermore, current studies on probiotic efficacy largely rely on indirect or relative readouts of intestinal bacterial burden. Herein, we directly quantify the probiotic effects of Ligilactobacillus murinus V10 and Escherichia coli Nissle 1917 (EcN 1917) against Klebsiella pneumoniae dysbiosis. Both L. murinus V10 and EcN demonstrated the ability to robustly protect against K. pnuemoniae-mediated dysbiosis throughout the length of the intestine, however, L. murinus V10 had a greater impact in the proximal intestine while EcN 1917 exerted a greater protective effect distally. The mechanistic underpinnings of both probiotic species remain elusive, however, the probiotic effect of EcN 1917 can at least in part be attributed to respiration using its high-affinity oxidase CydA. L. murinus V10 has strain-specific probiotic effects against Kp-39 dysbiosis in the proximal intestine. Further, dosing schedule of probiotics relative to Kp-39 (priority effect) was found to play a role in L. murinus V10-mediated protection but did not impact the probiotic action of EcN 1917. Finally, protection against dysbiotic expansion of K. pneumoniae did not necessarily translate directly to the effective prevention of K. pneumoniae mediated sepsis. We used transcriptomics and metabolomics to explore and identify potential mechanisms by which L. murinus V10 might exert its probiotic effects, but have not yet established the molecular basis of those effects. In total, we demonstrate how two disparate probiotic species colonize the murine neonatal intestine and interact with a clinically relevant pathogen in the context of neonatal dysbiosis, and how that does not necessarily translate to outcomes in the context of neonatal sepsis. Taken together, our data underscore the complex biological endeavor of probiotic intervention in the preterm intestine and the utility of applying community ecology as a framework for its analysis.
ProQuest ID
Recommended Citation
Hansen, Sierra, "Probiotic Biogeography In The Neonatal Intestine" (2025). All ETDs from UAB. 7358.
https://digitalcommons.library.uab.edu/etd-collection/7358
