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.

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