VCOM Louisiana Research Day Program

Biomedical Research

1 Alexandra Kuck, BS, OMS-II; 1 Corbin Sapp, BS, OMS-III; 1 Lauren Uram, BS, OMS-III; 2 Emma Kange, BS, OMS-III; 2 Pritty Dwivedy, BS, OMS-IV; 2 Ramu Anandakrishnan, PhD; 2 Robin Varghese, PhD; 3 Aline Andres, RD, PhD; 1 Melissa Lipsmeyer, MS, PhD 1 Edward Via College of Osteopathic Medicine-Louisiana, Monroe, Louisiana; 2 Edward Via College of Osteopathic Medicine-Virginia, Blacksburg, Virginia; 3 Arkansas Children’s Nutrition Center, Little Rock, Arkansas 06 EXPLORING THE FUNCTION OF THE BACTERIAL-DERVIVED METABOLITE INDOLE-3-PROPIONIC ACID IN PLACENTAL PHYSIOLOGY AND IT’S POTENTIAL PROTECTIVE ROLE AGAINST OBESITY-INDUCED PERTUBATIONS DURING PREGNANCY

Context: Indole-3-propionic acid (IPA) is a bacterial derived metabolite from the gut microbiome that has anti-inflammatory properties and has been shown to decrease oxidative stress in various tissues. With regard to metabolism, IPA is a known regulator of glucose homeostasis and is decreased in the serum of patients with Type 2 diabetes mellitus as well as in patients with obesity. While the molecular functions of IPA are characterized in some tissues, it’s role in female reproductive tissues remains unknown. Objective/Hypothesis: The objective of this study was to determine if placental IPA levels differed in women during the first trimester of pregnancy with overweight/obesity from normal weight counterparts. We also investigated if serum IPA levels were associated with specific dietary patterns as well as markers for glucose homeostasis, inflammation, or lipid metabolism. We furthered our investigation into the protective mechanism of IPA against obesity utilizing human trophoblastic cell lines cultured in adipocyte conditioned media in an in vitro model of obesity. We hypothesized IPA would alter metabolic pathways related to glucose metabolism, inflammation, and oxidative stress. Methods: Serum was collected from n=198

women during the first trimester of pregnancy between 10-12 weeks of gestation. IPA levels were measured by ultra-high performance liquid chromatography-high-resolution accurate mass analysis. Other analytes were measured utilizing various methods. Analyses of IPA associated with specific markers was conducted using simple linear regression models. Characterization of IPA functions in placental trophoblastic cells in our in vitro model of obesity was performed by RNAseq analysis. Results: Serum IPA levels were significantly decreased in women with overweight/obesity (BMI) as well as in women with higher adiposity (%Fat mass). A significant negative correlation was found between serum IPA and %FM. Serum IPA levels were also significantly correlated with dietary fiber intake, HOMA-IR (insulin resistance) and serum insulin. No other associations were significant. RNAseq analysis revealed that IPA significantly altered expression of genes related to inflammation, cellular migration and adhesion, collagen expression as well as other genes implicated in disorders of the placenta in response to an obesogenic environment. Conclusion: Serum IPA levels are diminished in pregnant women with higher adiposity and may reflect a disruption of the microbiome. IPA

levels are significantly associated with serum insulin and lower levels of insulin resistance demonstrating IPA may influence glucose homeostasis and insulin sensitivity during pregnancy. Our RNAseq analysis offers initial insight into the molecular mechanisms of IPA in placental cells. 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.

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