Date of Award
2023
Degree Name
Biomedical Sciences
College
Joan C. Edwards School of Medicine
Type of Degree
M.S.
Document Type
Thesis
First Advisor
Dr. Alip Borthakur, Committee Chairperson
Second Advisor
Dr. James Denvir
Third Advisor
Dr. Richard Egleton
Abstract
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.
Subject(s)
Indole – Research.
Cell differentiation – Research.
Obesity – Research.
Recommended Citation
Hart, James, "Gut microbial metabolite indole: a stimulator of enteroendocrine cell differentiation via activation of aryl hydrocarbon receptor" (2023). Theses, Dissertations and Capstones. 1817.
https://mds.marshall.edu/etd/1817
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Biomedical Informatics Commons, Human and Clinical Nutrition Commons, Medical Education Commons, Molecular, Genetic, and Biochemical Nutrition Commons