Louisiana Research Day Program Book 2025

Biomedical Research: Section 1

Janika Ernst, BS ,OMS-IV 1 ; Arooj Arif BS, MS, OMS-II 1 ; Jourdan Blair, BS, OMS-III 1 ; Emily Gregory BA, MA ,OMS-II 1 ; Shailie Shah, BS, OMSII 1 ; Lin Kang, PhD 1 ; Robin Varghese, PhD 2 ; Melissa EH Lipsmeyer, MS, PhD 1 1 VCOM-Louisiana; 2 VCOM-Virginia 1 INDOLE-3-PROPIONIC ACID, A METABOLITE OF THE GUT-MICROBIOME, ALTERS NUMEROUS BIOLOGICAL PROCESSES OF PLACENTAL CELLS IN AN IN VITRO MODEL OF OBESITY

Context: Obesity during pregnancy is associated with detrimental changes in placental function that lead to the development of complications such as gestational diabetes and preeclampsia as well as altered metabolism in the offspring. With the incidence of obesity reaching epidemic levels world-wide, it is imperative to find mechanisms to mitigate these risks during pregnancy. The gut-microbiome is a diverse system that regulates numerous body functions through the secretion of specific metabolites. Gut dysbiosis has recently emerged as one mechanism that contributes to placental dysfunction and clear associations between obesity and gut dysbiosis are evident. Indole-3-propionic acid (IPA) is a gut microbiome derived metabolite that has anti-inflammatory, anti-oxidative stress and glucose regulatory functions, all of which are dysregulated in obesity. Previous studies have found altered levels of IPA in both serum and placentas of women with obesity. Additionally, it was found that serum IPA levels are correlated with lower levels of adiposity, circulating insulin and insulin resistance. However, it remains unknown what the physiological functions of IPA are in the placenta and if it could have potential protective effects against perturbations caused by obesity.

Objective/Hypothesis: The objective of this study is to determine what physiological role IPA plays in the placenta and if IPA can protect against obesity-induced alterations in cell function. We hypothesize that physiological levels of IPA will reduce inflammatory markers, alleviate oxidative stress and modulate glucose uptake through altered insulin signaling in placental cells based on previously documented functions of IPA in other tissue types. Methods: We developed an in vitro model of obesity where two human placental cell lines, BeWo (choriocarcinoma) and HTR8 (normal immortalized trophoblasts) were cultured in media conditioned by mature human adipocytes (ACM) to mimic an obesogenic environment. RNA sequencing (RNAseq) analysis was used to determine acute gene expression changes due to a 24 hour treatment with either a control (DMSO), IPA (1uM, physiological levels), ACM, or ACM+IPA to evaluate if IPA can reverse transcriptional changes induced by ACM. Results: Initial RNAseq analysis revealed ACM induced changes in genes related HIPPO signaling, and other metabolic pathways in

BeWo cells while changes in folate biosynthesis, DNA replication and cell cycle were altered with ACM+IPA treatment. In HTR8 cells, ACM treatment induced changes in inflammatory and extracellular-matrix-related pathways while ACM+IPA treatment altered focal adhesion, extracellular-matrix interactions and regulation of actin cytoskeleton function. Interestingly, the PI3K-AKT pathway was a common target in both cell lines with changes dependent upon the presence or absence of IPA. Conclusion: Our RNAseq analysis offers initial insight into the molecular mechanisms of IPA in placental cells that include alterations in extra cellular matrix dynamics and folate metabolism. These are novel functions of IPA not identified in other cell types. Collectively, this study highlights the importance of a healthy gut microbiome and potentially serves as a window of opportunity to mitigate the onset or severity of disorders such as gestational diabetes by enhancing the gut microbiome prior to pregnancy.

Biomedical Research: Section 1

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2025 Research Recognition Day