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The intestine as an endocrine organ and the role of gut hormones in metabolic regulation
Abstract
Gut hormones orchestrate pivotal physiological processes in multiple metabolically active tissues, including the pancreas, liver, adipose tissue, gut and central nervous system, making them attractive therapeutic targets in the treatment of obesity and type 2 diabetes mellitus. Most gut hormones are derived from enteroendocrine cells, but bioactive peptides that are derived from other intestinal epithelial cell types have also been implicated in metabolic regulation and can be considered gut hormones. A deeper understanding of the complex inter-organ crosstalk mediated by the intestinal endocrine system is a prerequisite for designing more effective drugs that are based on or target gut hormones and their receptors, and extending their therapeutic potential beyond obesity and diabetes mellitus. In this Review, we present an overview of gut hormones that are involved in the regulation of metabolism and discuss their action in the gastrointestinal system and beyond.
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“The central ghrelin signaling plays a pivotal role in diverse physiological functions, including the regulation of food intake, hippocampal synaptic plasticity and neurogenesis, anxiety, depression, and cognitive function.”
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“GLP-1 is an incretin hormone produced by the EECs in response to ingested nutrients to stimulate glucose-dependent insulin secretion and suppress appetite.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [544]
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Calcium-Sensing Receptor Regulation of Gastrointestinal Hormone Secretion
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“These EEC peptide hormones govern diverse physiologic functions like nutrient digestion, gut motility, satiety, and insulin signaling [6,7].”
Self-citationRole of exosomes in gastrointestinal physiology and pathophysiology
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Effects of microplastics on the intestines
Jarmakiewicz-Czaja, S., Ferenc, K., Sokal-Dembowska, A., Wojdyła, D., & Filip, R. (2026) · BMC Gastroenterology · doi:10.1186/s12876-026-04749-x · Cited by 4
“Additionally, EEC can be activated through transient receptor potential ankyrin A1 (Trpa1), as a result of the detection of intestinal bacteria, which can cause the activation of intestinal neurones [60, 61].”
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“By integrating multiomic data into these knowledge graphs, the ecosystem can generate novel insights into the gut – brain – sleep axis — such as the in fl uence of gut-derived hormones on sleep architecture or the role of speci fi c microbial metabolites in circadian rhythm regulation (85, 89).”
The gut–joint axis in osteoarthritis
Wei, J. H., Zhang, Y., Xie, C., Lei, G., & Zeng, C. (2026) · Nature Reviews Rheumatology · doi:10.1038/s41584-026-01378-2 · Cited by 5
“…several major gut functions: its endocrine role as the body’s largest hormone-producing organ (leading to impaired enteroendocrine signalling) 57,58 , its barrier role (causing increased intestinal permeability) 59 and its immunological role as a primary immune outpost (driving systemic…”
InfluentialGut microbiota in health and disease
Li, Y. N., Xiao, X., Jiang, X., Li, X., WANG, W., & Lin, R. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00512-6 · Cited by 6
“In the endocrine sys-tem, the microbiota influences incretin secretion, including GLP-1, PYY, and glucose-dependent insulinotropic polypeptide (GIP), contributing to glycemic stability [85, 86].”
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Incretin Signaling Neighborhoods and Adverse Drug Reactions
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Agrin at the crossroads of aging: A pleiotropic regulator in age-related diseases
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Diabetes treatment by conversion of gut epithelial cells to insulin‐producing cells
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Glutamate from the microbiome controls host metabolism
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Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells
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Stress, microbiota, and the gut–brain axis in mental and digestive health
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Digestibility of starchPreprint
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Intestinal enteroendocrine cell subtype differentiation and hormone production in zebrafishPreprint
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Self-citationEndocrine Properties of Microbiota
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“In addition to being engaged in the digestion of food, the GIT also performs endocrine functions [119, 120, 122].”
Porcine jejunal-derived extracellular vesicles participate in the regulation of lipid metabolism
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“The intestine, as an important organ for transmitting nutritional signals from external sources, plays a significant role in metabolic regulation [6].”
Intestinal Epithelial-Derived Exosomes Under Cold Stimulation Promote Adipose Thermogenesis
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Regulation of appetite via gut microbiota-modulated calcium ion channels: focus on tea polyphenols
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Metadata
- Authors
- Bany Bakar, R., Reimann, F., & Gribble, F. M.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Gribble, Fiona M.
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2023-08-25
- Volume
- 20
- Issue
- 12
- Pages
- 784-796
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- OpenAlex
- W4386168026
- Cited by
- 144
- References
- 223
- Citations by year
- 2026: 39 · 2025: 64 · 2024: 40 · 2023: 1
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (220271/Z/20/Z)
- Medical Research Council (MC_UU_00014/3)
- Biotechnology and Biological Sciences Research Council (1799260)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- gastrointestinal hormones, enteroendocrine cells, metabolic regulation, obesity, type 2 diabetes, organ crosstalk, digestive physiology, bioactive peptides
- MeSH terms
- Diabetes Mellitus, Type 2, Gastrointestinal Hormones, Humans, Intestines, Obesity, Gastrointestinal Tract
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