Role of ghrelin in the pathophysiology of gastrointestinal disease
Open accessAbstract
Ghrelin is a 28-amino-acid peptide that plays multiple roles in humans and other mammals. The functions of ghrelin include food intake regulation, gastrointestinal (GI) motility, and acid secretion by the GI tract. Many GI disorders involving infection, inflammation, and malignancy are also correlated with altered ghrelin production and secretion. Although suppressed ghrelin responses have already been observed in various GI disorders, such as chronic gastritis, Helicobacter pylori infection, irritable bowel syndrome, functional dyspepsia, and cachexia, elevated ghrelin responses have also been reported in celiac disease and inflammatory bowel disease. Moreover, we recently reported that decreased fasting and postprandial ghrelin levels were observed in female patients with functional dyspepsia compared with healthy subjects. These alterations of ghrelin responses were significantly correlated with meal-related symptoms (bloating and early satiation) in female functional dyspepsia patients. We therefore support the notion that abnormal ghrelin responses may play important roles in various GI disorders. Furthermore, human clinical trials and animal studies involving the administration of ghrelin or its receptor agonists have shown promising improvements in gastroparesis, anorexia, and cancer. This review summarizes the impact of ghrelin, its family of peptides, and its receptors on GI diseases and proposes ghrelin modulation as a potential therapy.
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Ghrelin has been associated with enhanced rate of gastric emptying.
“Ghrelin has been associated with enhanced rate of gastric emptying (Levin et al., 2006; Cheung and Wu, 2013).”
From Thyroid disorders and gastrointestinal dysmotility: an old association (2024) · cites this paper as Cheung and Wu, 2013
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Gastrointestinal Dysfunction in Parkinson’s Disease
Fasano, A., Visanji, N. P., Liu, L. W. C., Lang, A. E., & Pfeiffer, R. F. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00007-1 · Cited by 1,016 · see citing works
Cancer cachexia, mechanism and treatment
Aoyagi, T., Terracina, K. P., Raza, A., Matsubara, H., & Takabe, K. (2015) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v7.i4.17 · Cited by 439 · see citing works
Ghrelin and motilin receptors as drug targets for gastrointestinal disorders
Sanger, G. J., & Furness, J. B. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.163 · Cited by 128 · see citing works
Ghrelin and Obesity: Identifying Gaps and Dispelling Myths. A Reappraisal
Makris, M. C., Alexandrou, A. P., Papatsoutsos, E. G., Malietzis, G. A., Tsilimigras, D. I., Guerron, A. D., & Moris, D. (2017) · In Vivo · doi:10.21873/invivo.11168 · Cited by 97 · see citing works
Ghrelin: ghrelin as a regulatory Peptide in growth hormone secretion.
Khatib, N., Gaidhane, S., Gaidhane, A., Khatib, M., Simkhada, P., Gode, D., & Zahiruddin, Q. (2014) · Journal of clinical and diagnostic research : JCDR · doi:10.7860/jcdr/2014/9863.4767 · Cited by 100 · see citing works
Woźniak, D., Cichy, W., Przysławski, J., & Drzymała-Czyż, S. (2021) · Advances in Medical Sciences · doi:10.1016/j.advms.2021.05.003 · Cited by 74 · see citing works
Gastrointestinal neuroendocrine peptides/amines in inflammatory bowel disease
El‐Salhy, M., Solomon, T., Hausken, T., Gilja, O. H., & Hatlebakk, J. G. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i28.5068 · Cited by 69 · see citing works
Ghrelin as a Promising Therapeutic Option for Cancer Cachexia
Khatib, M. N., Gaidhane, A. M., Gaidhane, S., & Zahiruddin, Q. S. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000492559 · Cited by 59 · see citing works
The Gut and Nonmotor Symptoms in Parkinson's Disease
Klingelhoefer, L., & Reichmann, H. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.05.027 · Cited by 53 · see citing works
Tse, G., Lai, E. T. H., Yeo, J. M., Tse, V., & Wong, S. H. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00182 · Cited by 51 · see citing works
Gastroparesis in Parkinson Disease: Pathophysiology, and Clinical Management
Soliman, H., Coffin, B., & Gourcerol, G. (2021) · Brain Sciences · doi:10.3390/brainsci11070831 · Cited by 52 · see citing works
Thyroid disorders and gastrointestinal dysmotility: an old association
Xu, G.-M., Hu, M.-X., Li, S.-Y., Ran, X., Zhang, H., & Ding, X.-F. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1389113 · Cited by 43 · see citing works
Obesity-associated Pathways of Anthocyanins
Yıldız, E., Güldaş, M., Ellergezen, P. H., Acar, A. G., & Gürbüz, O. (2020) · Food Science and Technology · doi:10.1590/fst.39119 · Cited by 36 · see citing works
Chromogranin A and other enteroendocrine markers in inflammatory bowel disease
Massironi, S., Zilli, A., Cavalcoli, F., Conte, D., & PERACCHI, M. (2016) · Neuropeptides · doi:10.1016/j.npep.2016.01.002 · Cited by 32 · see citing works
Ghrelin administration suppresses inflammation‐associated colorectal carcinogenesis in mice
Kawaguchi, M., Kanemaru, A., Fukushima, T., Yamamoto, K., Tanaka, H., Haruyama, Y., Itoh, H., Matsumoto, N., Kangawa, K., Nakazato, M., et al. (2015) · Cancer Science · doi:10.1111/cas.12725 · Cited by 32 · see citing works
Contribution of ghrelin to functional gastrointestinal disorders’ pathogenesis
Koutouratsas, T., Kalli, T., Karamanolis, G. P., & Gazouli, M. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i5.539 · Cited by 31 · see citing works
Altered Functional Connectivity of the Amygdala and Sex Differences in Functional Dyspepsia
Zeng, F., Sun, R., He, Z., Chen, Y., Du, L., Yin, T., Liu, X., Yang, Y., Ma, P., Qu, Y., et al. (2019) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000046 · Cited by 31 · see citing works
Ghrelin and Leptin Have a Complex Relationship with Risk of Barrett’s Esophagus
Thomas, S. J., Almers, L. M., Schneider, J. L., Graham, J. L., Havel, P. J., & Corley, D. A. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3867-6 · Cited by 24 · see citing works
Mitoiu, B. I., Nartea, R., & Miclăuș, R. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158067 · Cited by 23 · see citing works
Yüksel, B., Demiral, İ., Zeybek, Ü., Çelik, F., Buyru, F., Yeh, J., & Baştu, E. (2020) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2019.0083 · Cited by 23 · see citing works
The Role ofH. pyloriCagA in Regulating Hormones of Functional Dyspepsia Patients
Meng, W. P., Wang, Z., Deng, J., Liu, Y., Deng, M., & Lü, M.-H. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/7150959 · Cited by 23 · see citing works
Growth hormone secretagogue receptor is important in the development of experimental colitis
Liu, Z.-Z., Wang, W., Li, Q., Tang, M., Li, J., Wu, W.-T., Wan, Y.-H., Wang, Z., Bao, S., & Fei, J. (2015) · Cell & Bioscience · doi:10.1186/s13578-015-0002-5 · Cited by 21 · see citing works
Novel therapeutic agents in neurogastroenterology: advances in the past year
Camilleri, M. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12386 · Cited by 19 · see citing works
Russo, F., Chimienti, G., Clemente, C., Ferreri, C., Orlando, A., & Riezzo, G. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-1128-2 · Cited by 18 · see citing works
Cavalheiro, E. K. F. F., Costa, A. B., Salla, D. H., da Silva, M. R., Mendes, T. F., da Silva, L. E., Turatti, C. D. R., de Bitencourt, R. M., & Rezin, G. T. (2021) · Cannabis and Cannabinoid Research · doi:10.1089/can.2021.0016 · Cited by 19 · see citing works
Tian, P., Lu, X., Jin, N., & Shi, J. (2020) · Cell Biology International · doi:10.1002/cbin.11362 · Cited by 16 · see citing works
Evaluation of Appetite-Regulating Hormones ın Young Children with Autism Spectrum Disorder
Sadıç, Ç. Ç., Bi̇lgi̇ç, A., Kılınç, İ., Oflaz, M. B., & Baysal, T. (2020) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-020-04579-0 · Cited by 14 · see citing works
Gewehr, M. C. F., Silvério, R., Neto, J. C. R., Lira, F. S., Reckziegel, P., & Ferro, E. S. (2020) · Molecules · doi:10.3390/molecules25051093 · Cited by 14 · see citing works
Weight Regain after Metabolic Surgery: Beyond the Surgical Failure
Salazar, J. J., Durán, P., Garrido, B., Parra, H., Hernández, M., Cano, C., Áñez, R., García-Pacheco, H., Cubillos-Valencia, G., Vasquez, N., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13041143 · Cited by 13 · see citing works
Mareș, C. R., Săsăran, M. O., & Mărginean, C. O. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1431660 · Cited by 13 · see citing works
Graybeal, A. J., Willis, J. L., Morales, E., Tinsley, G. M., Messiah, S. E., & Shah, M. (2022) · Nutrition · doi:10.1016/j.nut.2022.111815 · Cited by 12 · see citing works
Rodríguez-García, J. L., & Carmona-Sánchez, R. (2016) · Revista de Gastroenterología de México (English Edition) · doi:10.1016/j.rgmxen.2016.06.017 · Cited by 12 · see citing works
Relationship between irritable bowel syndrome and plasma and tissue ghrelin levels
Şahin-Eryılmaz, G., Başak, K., Madenci, Ö. Ç., Koç, H., Tüzün, S., Dolapçıoğlu, C., Ahıshalı, E., & Dabak, M. R. (2018) · The Turkish Journal of Gastroenterology · doi:10.5152/tjg.2018.17593 · Cited by 12 · see citing works
Russo, F., Chimienti, G., Linsalata, M., Clemente, C., Orlando, A., & Riezzo, G. (2016) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000000760 · Cited by 11 · see citing works
Hijaz, N. M., Friesen, C. A., Schurman, J. V., Pearce, R. E., & Abdel‐Rahman, S. M. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12591 · Cited by 10 · see citing works
Dimino, J., & Kuo, B. (2025) · Diagnostics · doi:10.3390/diagnostics15070935 · Cited by 9 · see citing works
Enterohormonal disturbances in colorectal cancer patients
Zygulska, A. L., Furgała, A., Krzemieniecki, K., Kaszuba-Zwoińska, J., & Thor, P. (2017) · Neoplasma · doi:10.4149/neo_2017_313 · Cited by 9 · see citing works
Ghrelin upregulates PepT1 activity in the small intestine epithelium of rats with sepsis
Liu, J., Shi, B., Shi, K., Ma, G., Zhang, H., Lou, X., Liu, H., Wan, S.-X., & Liang, D. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.026 · Cited by 8 · see citing works
Rodríguez-García, J. L., & Carmona-Sánchez, R. (2016) · Revista de Gastroenterología de México · doi:10.1016/j.rgmx.2016.02.009 · Cited by 7 · see citing works
Therapeutic potential of ghrelin/GOAT/GHSR system in gastrointestinal disorders
Ma, Y., Yan, Q., Wang, P., Guo, W., & Yu, L. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1422431 · Cited by 6 · see citing works
Enhancement of ghrelin-signaling system by Rikkunshi-To attenuates teriparatide-induced pica in rats
Yamamoto, K., Isogai, Y., Ishida, T., & Hagihara, K. (2018) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2018.05.003 · Cited by 6 · see citing works
Kras, K., Ropka‐Molik, K., Muszyński, S., & Arciszewski, M. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010533 · Cited by 5 · see citing works
Transition of a pancreatic neuroendocrine tumor from ghrelinoma to insulinoma: a case report.
Chauhan, A., Ramirez, R. A., Stevens, M., Burns, L. A. K., & Woltering, E. A. (2015) · PubMed Central · doi:10.3978/j.issn.2078-6891.2014.113 · Cited by 4 · see citing works
Krauthammer, A., Berger, T. D., Nachum, N. L., Granot, M., Barshack, I., & Weiss, B. (2025) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1002/jpn3.70254 · Cited by 2 · see citing works
Ahmad, Y., Wasan, R., Perchik, J. D., & Nanda, N. C. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15124430 · Cited by 2 · see citing works
Kaiya, H. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820649-2.00083-8 · Cited by 2 · see citing works
Obesity, Immunology and Obesity Surgery
Özmen, M. M. (2016) · Advances in Obesity Weight Management & Control · doi:10.15406/aowmc.2016.04.00080 · Cited by 2 · see citing works
Altan, S., DÖNMEZ, K., Altan, F., & Alkan, F. (2018) · TURKISH JOURNAL OF VETERINARY AND ANIMAL SCIENCES · doi:10.3906/vet-1803-3 · Cited by 2 · see citing works
Czkwianianc, E., Kolejwa, M., Bossowski, A. T., Wawrusiewicz‐Kurylonek, N., Głowacka, E., Makosiej, A., Gościk, J., Socha‐Banasiak, A., & Makosiej, R. (2021) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003124 · Cited by 2 · see citing works
Farmer, A. D., & Aziz, Q. (2015) · Yamada's Textbook of Gastroenterology · doi:10.1002/9781118512074.ch14 · Cited by 2 · see citing works
Damiens, Q., Mille, V., Faure, J., Toussirot, E., Valnet-Rabier, M., & Béreau, M. (2026) · Journal of Parkinson's Disease · doi:10.1177/1877718x261432743 · Cited by 1 · see citing works
Wang, Z., Cao, Q., Xiang, C., Yu, C., Xie, C. H., Luo, B., Zhu, D., Xu, Y., Chen, Y., Wu, T., et al. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15803 · Cited by 1 · see citing works
KLINISCHE CHEMIE UND LABORATORIUMSMEDIZIN
Schmitz, G., & Medizin, F. F. (2014) · Cited by 1 · see citing works
CORRELATION OF GHRELIN AND C-PEPTIDE HORMONES AND SOME OTHER BIOCHEMICAL FACTORS WITH WOMEN OBESITY
Hayder, E. W., & Hadi, E. A. (2021) · Egyptian Journal of Chemistry · doi:10.21608/ejchem.2021.80170.3965
春間賢, 裕明, 楠., & 眞部紀明 (2014) · 日本消化機病學會雜誌. 乙 · doi:10.11405/nisshoshi.111.1049
Passos, M., & Ramos, A. (2017) · doi:10.22288/978852045650700004
Mechanism of gastrointestinal injury in COVID-19 and potential use of ghrelin therapy
Tian, J.-G., Liu, X.-P., Zhang, B., Zhang, J., Sun, G.-B., & Li, M. (2023) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v31.i11.431
Cellular and molecular mechanisms involved in colonic disorders
Kaur, S., Singh, A., Kaur, H., Singh, J., & Bhatti, R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-14044-0.00007-7
The Effect of Ghrelin on Gastrointestinal Function: From Basic Research to Clinical Application
王, 若. (2024) · Journal of Clinical Personalized Medicine · doi:10.12677/jcpm.2024.32042
Hussein, A., Gareeballah, A., Amer, A. M., Alshoabi, S. A., Gameraddin, M. B., Elzaki, M. M., Alsharif, W. M., Alhazmi, F. H., Abouraida, R. A., Alsultan, K. D., et al. (2024) · BMC Gastroenterology · doi:10.1186/s12876-024-03529-9
Emerging bioelectronics and optogenetics for neurogastroenterology
Liu, H., Luo, W., Xu, M., Zhang, S., Xue, J., Chen, Q., Zhao, Y., Hu, N., & Gao, Z. (2025) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2025.117795
Ghrelin Levels and Disease Localization in Inflammatory Bowel Disease: A Correlation Study
Cesur, S., Değerli, E., Ürün, Y. Y., & Karaali, Z. (2025) · Sakarya Medical Journal · doi:10.31832/smj.1679691
Uzun, N., Bi̇lgi̇ç, A., Ferahkaya, H., Katırcıoğlu, D. Ö., Kılınç, İ., & Oflaz, M. B. (2026) · International Journal of Developmental Disabilities · doi:10.1080/20473869.2026.2660339
Elall, M. S. A., Elfakhry, A. A., Atwa, M. A., & Abozeid, F. (2026) · International Journal of Noncommunicable Diseases · doi:10.4103/jncd.jncd_231_25
Brain barriers as checkpoints in endocrine regulation of body homeostasis
Kang, D. Y., Lee, M. J., Kim, S. C., Park, S., An, J. H., Pyo, C. H., Kim, Y., Jeong, J., Park, Y., Yeo, M., et al. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261444202
Gerstmayer, S. M., Margarit, I. S., Rytter, A., Bøgh, K. L., Wessel, I., Sporring, M. L., & Jalili, M. (2026) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2026.105062
- Authors
- Cheung, C. K., & Wu, J. C.-Y.
- Affiliations
- Chinese University of Hong Kong (HK)
- ORCID
- Cheung, Cynthia K.
- Venue
- Gut and Liver
- Published
- 2013-09-15
- Volume
- 7
- Issue
- 5
- Pages
- 505-512
- ISSN
- 1976-2283 (ISSN-L)
- 2005-1212
- PMC
- PMC3782663
- OpenAlex
- W2094745009
- Cited by
- 68
- References
- 86
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 9 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 9 · 2015: 10 · 2014: 4
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Gut and Liver (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, gastrointestinal diseases, ghrelin receptor agonist, food intake regulation, gastrointestinal motility, gastric acid secretion, Helicobacter pylori infection, chronic gastritis, irritable bowel syndrome, functional dyspepsia, celiac disease, inflammatory bowel disease, cachexia, gastroparesis, anorexia, cancer
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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