How GLP-1 and GIP Hormone Receptors in the Gut Influence Immune Function and Inflammation

What the researchers found

The review identifies that GLP-1 receptors are expressed on multiple types of intraepithelial lymphocytes in the gut, including natural (TCRαβ and TCRγδ) and induced (TCRαβ+CD4+ and TCRαβ+CD8αβ+) populations. Both the body's own GLP-1 signaling and pharmacological GLP-1R activation influence local gut inflammation, systemic inflammation, the gut microbiome, whole-body metabolism, and GLP-1 bioavailability itself.

GIPR signaling has been shown to affect the production of blood cells from bone marrow (hematopoiesis), but its specific role in gut immune function remains poorly understood. The authors also highlight a significant gap in the literature regarding how biological sex influences these signaling pathways.

Why it matters

GLP-1 receptor agonists (like semaglutide) and dual GLP-1R/GIPR agonists (like tirzepatide) are among the most widely prescribed medications for diabetes and obesity. This review highlights that these drugs may have important effects on gut immune function and inflammation that are not yet fully understood — effects that could be relevant to the millions of people currently taking them.

How the study worked

This is a narrative review synthesizing preclinical (animal model) and clinical evidence on GLP-1R and GIPR signaling in gut immunology. The authors examined published literature on incretin hormone receptors expressed on intestinal immune cells and their roles in inflammation and metabolism.

What this study cannot tell us

As a narrative review, this paper synthesizes existing research rather than presenting new experimental data. The authors themselves note significant gaps in the literature, particularly around sex-based differences in GLP-1R and GIPR signaling. Much of the evidence comes from preclinical animal models, which may not fully translate to humans. The review does not include a systematic search methodology.

How to read the evidence

This is a narrative review article that synthesizes preclinical and clinical evidence without conducting new experiments or following systematic review methodology. While it provides valuable synthesis and identifies important gaps, it does not generate new primary data.

When this study was published

Published in 2024, this review is highly current and addresses the rapidly evolving understanding of incretin-based therapies that are now among the most prescribed medications globally.

The bigger picture

As GLP-1-based medications become some of the most prescribed drugs worldwide, understanding their effects beyond blood sugar and weight is critical. This review connects incretin biology to gut immunology — a rapidly growing field — and suggests that these hormones may play maintenance roles during normal fasting and feeding cycles. The findings could eventually inform how clinicians monitor and manage gut health in patients on incretin-based therapies.

Questions still open

• How do GLP-1R agonist medications specifically alter gut immune cell populations and inflammation in human patients?
• Do men and women respond differently to incretin-based therapies in terms of gut immune modulation?
• Could targeting GLP-1R on gut immune cells become a strategy for treating inflammatory bowel diseases?

Common questions

Read the original research

Immunomodulation and inflammation: Role of GLP-1R and GIPR expressing cells within the gut.

Peptides, 176, 171200

Citation

Morrow, Nadya M; Morissette, Arianne; Mulvihill, Erin E. (2024). Immunomodulation and inflammation: Role of GLP-1R and GIPR expressing cells within the gut.. Peptides, 176, 171200. https://doi.org/10.1016/j.peptides.2024.171200