Date of Award
Joan C. Edwards School of Medicine
Type of Degree
Dr. Alip Borthakur, Committee Chairperson
Dr. James Denvir
Dr. Richard Egleton
Enteroendocrine cells (EECs) regulate energy balance and glucose homeostasis by releasing hormones in response to food intake. Dysregulated EEC differentiation is observed in obesity, while gut microbiota metabolites influence this process. Here, we investigated the role of indole, a biologically active gut microbial metabolite, in EEC differentiation through aryl hydrocarbon receptor (AhR) activation. Human intestinal organoids derived from jejunal mucosal biopsies were exposed to indole. Indole treatment significantly increased mRNA levels of chromogranin A, an EEC marker. The effect was reversed by an AhR antagonist, indicating AhR involvement. Indole also upregulated AhR target gene mRNA levels. These findings highlight the potential of AhR activation as a novel pathway by which gut microbial metabolites, such as indole, stimulate EEC differentiation. Understanding the mechanisms underlying EEC differentiation may offer insights into therapeutic strategies for metabolic disorders associated with impaired EEC function.
Indole – Research.
Cell differentiation – Research.
Obesity – Research.
Hart, James, "Gut microbial metabolite indole: a stimulator of enteroendocrine cell differentiation via activation of aryl hydrocarbon receptor" (2023). Theses, Dissertations and Capstones. 1817.