MSc Thesis Defense: Sümeyra Nuran Özmen, MODULATION OF BRAIN BARRIER FUNCTION BY MICROBIOTA-DERIVED FACTORS IN CEREBRAL ISCHEMIA, Date & Time: June 25, 2026 – 2:00 PM, Place: FENS G032
MODULATION OF BRAIN BARRIER FUNCTION BY MICROBIOTA-DERIVED FACTORS IN CEREBRAL ISCHEMIA
Sümeyra Nuran Özmen
Molecular Biology, Genetics and Bioengineering, MSc Thesis, 2026
Thesis Jury
Asst. Prof. Nur Mustafaoglu Varol (Thesis Advisor)
Asst. Prof. Duygu Kuzuoğlu Öztürk
Assoc. Prof. Fatima Susanna F. Aerts Kaya
Date & Time: June 25th, 2026 – 2.00 PM
Place: FENS G032
Keywords: gut-brain axis, ischemic stroke, blood-brain barrier, metabolite, induced pluripotent stem cell (iPSC), in vitro models
Abstract
Recent studies have highlighted the critical role of the gut-brain axis in the development and progression of brain disorders, including cerebral ischemia. Gut microbiota-derived metabolites have been shown to modulate both blood-brain barrier (BBB) and intestinal barrier functions under physiological and pathological conditions, including stroke. Human cell-based in vitro models of the gut and BBB offer promising alternatives to animal models for investigating these complex interactions. In this study, transwell and microfluidic chip platforms were employed to recapitulate human gut and BBB physiology. The BBB models were established using primary human astrocytes and pericytes together with human induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (iBMECs). To model ischemia in vitro, BBB models were exposed to hypoxia, lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα). In addition, two microbiota-related metabolites, tauroursodeoxycholic acid (TUDCA) and lactate, were evaluated using both BBB transwell and microfluidic chip models. Furthermore, the gut barrier model established by CaCo-2 cells on transwells to investigate direct interactions between the gut and the BBB. For this purpose, filtrates obtained from fecal bacteria isolated from healthy mice and mice subjected to middle cerebral artery occlusion (MCAO) were introduced separately to the gut and BBB models. In addition, samples collected from the gut model following exposure to these bacterial filtrates were subsequently applied to the BBB model to evaluate the metabolic communication in the gut-brain axis. The effects of these treatments were assessed through transendothelial electrical resistance (TEER) measurement, permeability assays and immunofluorescence analyses. The findings indicate that gut microbiota-derived factors influence gut barrier and BBB integrity and function under healthy and stroke-like conditions. Further investigations using physiologically relevant gut and BBB models, combined with a broader range of microbiota-derived metabolites, may provide valuable insights into the development of therapeutic strategies targeting the gut-brain axis in cerebral ischemia.