VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 1

Lucia Conlon, BS, OMS-II; Janika Ernst, BS, OMS-III; Claire Travis, MS, OMS-II; Lin Kang, PhD; and Melissa Lipsmeyer, MS, PhD VCOM-Louisiana 5 EXPLORING THE POTENTIAL PROTECTIVE ROLE OF THE BACTERIAL-DERIVED METABOLITE INDOLE-3-PROPIONIC ACID AGAINST OBESOGENIC INSULTS IN PLACENTA CELL LINES

Background: 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 overweight/obesity and 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: The objective of this study is to

determine what physiological role IPA plays in the placenta and if IPA can protect against obesogenic insults such as hyperinsulinemia, oxidative stress, lipid peroxidation and inflammation which contribute to placental pathology. 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. Methods: For this study, 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). RNA sequencing (RNAseq) analysis was used to determine acute effects of IPA treatment after 24 hours in the presence and absence of ACM. We further examined the influence of IPA on insulin signaling with physiological and hyperinsulinemia levels of insulin at 24 and 72 hours utilizing QPCR and western blot analyses. Results: RNAseq analysis revealed treatment with physiological levels of IPA induced changes in genes associated with normal placental function, autophagy and inflammatory mediated processes and other pathways. Subsequent

studies on the impact of IPA on insulin signaling, glucose uptake and oxidative stress are ongoing. Conclusions: Our RNAseq analysis offers initial insight into the molecular mechanisms of IPA in placental cells. Future analyses will investigate the potential role of insulin signaling, glucose homeostasis and oxidative stress. 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 pregnancy-related disorders such as gestational diabetes by enhancing the gut microbiome prior to pregnancy.

17 2024 Via Research Recognition Day