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Scratching the Surface: Exploring Gastrointestinal Serotonin’s Impact on Chronic Pruritus in Irritable Bowel Syndrome and Dyspepsia

DOI: 10.4236/ojcd.2025.151002, PP. 8-27

Keywords: Serotonin Dysregulation, Chronic Pruritus, Gut-Brain Axis, Irritable Bowel Syndrome, Functional Dyspepsia, Neurogenic Inflammation, Serotonin Receptor Modulators, Microbiota-Targeted Therapies

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Abstract:

Background and Aims: Gastrointestinal-derived serotonin (5-HT) plays a crucial role in the enteric nervous system and has been identified as a key mediator in the pathogenesis of chronic pruritus associated with irritable bowel syndrome (IBS) and functional dyspepsia (FD). Dysregulated serotonin signaling, driven by altered enterochromaffin cell activity and abnormal serotonin reuptake, contributes to gut-brain axis dysfunction and sensitizes peripheral nerves, leading to increased pruritic sensations. This review explores the interplay between serotonin dysregulation, neurogenic inflammation, and chronic pruritus in IBS and FD, with an emphasis on potential therapeutic interventions. This review aims to address the gap in understanding the specific mechanisms by which serotonin dysregulation affects pruritus and gastrointestinal function, offering new insights into potential therapeutic approaches. Methods: A comprehensive literature review was conducted to examine the role of serotonin dysregulation in chronic pruritus associated with IBS and FD. Relevant studies were analyzed to assess serotonin’s impact on visceral hypersensitivity, systemic inflammation, and neurogenic skin responses. Additionally, the effectiveness of serotonin receptor modulators, systemic agents such as gabapentinoids, and microbiota-targeted therapies in mitigating pruritic symptoms was evaluated. Results: Dysregulated serotonin signaling in IBS and FD exacerbates visceral hypersensitivity and systemic inflammation, contributing to neurogenic inflammation in the skin and the release of pruritogenic mediators, including substance P and histamine. This persistent itch response significantly reduces patients’ quality of life. Evidence suggests that serotonin receptor modulators, particularly 5-HT3 and 5-HT4 antagonists, can alleviate pruritic symptoms by addressing both gastrointestinal motility and pruritus-associated pathways. Additionally, systemic agents like gabapentinoids provide complementary neural desensitization. Emerging data indicate that gut microbiome imbalances in IBS and FD influence serotonin production, highlighting a potential role for microbiota-targeted therapies in reducing pruritus severity. Conclusions: Addressing the complex interaction between gastrointestinal serotonin dysregulation, neurogenic inflammation, and chronic pruritus is essential for advancing therapeutic strategies. A comprehensive approach targeting the gut-brain-skin axis has the potential to redefine pruritus management

 References

[1]  Ferreira, B.R., Katamanin, O.M., Jafferany, M. and Misery, L. (2024) Psychodermatology of Chronic Pruritus: An Overview of the Link between Itch and Distress. Dermatology and Therapy, 14, 1799-1809.
https://doi.org/10.1007/s13555-024-01214-z
[2]  Brizuela, M., Castro, J., Harrington, A.M. and Brierley, S.M. (2021) Pruritogenic Mechanisms and Gut Sensation: Putting the “Irritant” into Irritable Bowel Syndrome. American Journal of Physiology-Gastrointestinal and Liver Physiology, 320, G1131-G1141.
https://doi.org/10.1152/ajpgi.00331.2020
[3]  Parvizi, M.M., Shabani, M., Saki, N., Rajabi, S., Rampp, T. and Pasalar, M. (2021) Association of Functional Dyspepsia with Selected Dermatology Complaints and Sleep Disturbances Based on Traditional Persian Medicine. Iranian Journal of Dermatology, 24, 110-116.
[4]  Zhou, Q.Q. and Verne, G.N. (2011) New Insights into Visceral Hypersensitivity—Clinical Implications in IBS. Nature Reviews Gastroenterology & Hepatology, 8, 349-355.
https://doi.org/10.1038/nrgastro.2011.83
[5]  Brizuela, V., Cuesta, C., Bartolelli, G., Abdosh, A.A., Abou Malham, S., Assarag, B., et al. (2021) Availability of Facility Resources and Services and Infection-Related Maternal Outcomes in the WHO Global Maternal Sepsis Study: A Cross-Sectional Study. The Lancet Global Health, 9, e1252-e1261.
https://doi.org/10.1016/s2214-109x(21)00248-5
[6]  Wang, X.X., Li, Y.F., Wu, L.J., Xiao, S.J., Ji, Y.R., Tan, Y., et al. (2021) Dysregulation of the Gut-Brain-Skin Axis and Key Overlapping Inflammatory and Immune Mechanisms of Psoriasis and Depression. Biomedicine & Pharmacotherapy, 137, Article 111065.
https://doi.org/10.1016/j.biopha.2020.111065
[7]  Martins, A.M., Ascenso, A., Ribeiro, H.M. and Marto, J. (2020) The Brain-Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System. Cells, 9, Article 796.
https://doi.org/10.3390/cells9040796
[8]  Margoob, M., Kouser, S. and Jan, N. (2024) Serotonin: The Link between Gut Microbiome and Brain. In: Fatima-Shad, K., Ed., Serotonin-Neurotransmitter and Hormone of Brain, Bowels and Blood, IntechOpen, 9-10.
https://doi.org/10.5772/intechopen.1003826
[9]  De Pessemier, B., Grine, L., Debaere, M., Maes, A., Paetzold, B. and Callewaert, C. (2021) Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms, 9, Article 353.
https://doi.org/10.3390/microorganisms9020353
[10]  Morita, T., McClain, S.P., Batia, L.M., Pellegrino, M., Wilson, S.R., Kienzler, M.A., et al. (2015) HTR7 Mediates Serotonergic Acute and Chronic Itch. Neuron, 87, 124-138.
https://doi.org/10.1016/j.neuron.2015.05.044
[11]  Park, H., Ahn, S., Lee, H., Hahm, D., Kim, K. and Yeom, M. (2021) Acupuncture Ameliorates Not Only Atopic Dermatitis-Like Skin Inflammation but Also Acute and Chronic Serotonergic Itch Possibly through Blockade of 5-HT2 and 5-HT7 Receptors in Mice. Brain, Behavior, and Immunity, 93, 399-408.
https://doi.org/10.1016/j.bbi.2021.01.027
[12]  Chen, G., Chen, Z.-M., Fan, X.-Y., Jin, Y.-L., Li, X., Wu, S.-R., et al. (2020) Gut–brain–Skin Axis in Psoriasis: A Review. Dermatology and Therapy, 11, 25-38.
https://doi.org/10.1007/s13555-020-00466-9
[13]  Guzel, T. and Mirowska-Guzel, D. (2022) The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy. Molecules, 27, Article 1680.
https://doi.org/10.3390/molecules27051680
[14]  Dobrek, Ł. and Thor, P.J. (2009) Pathophysiological Concepts of Functional Dyspep-Sia and Irritable Bowel Syndrome: Future Pharmacotherapy. Acta Poloniae Pharma-Ceutica-Drug Research, 66, 447-460.
[15]  Koopman, N., Katsavelis, D., Ten Hove, A., Brul, S., de Jonge, W. and Seppen, J. (2021) The Multifaceted Role of Serotonin in Intestinal Homeostasis. International Journal of Molecular Sciences, 22, Article 9487.
https://doi.org/10.3390/ijms22179487
[16]  Najjar, S.A., Hung, L.Y. and Margolis, K.G. (2023) Serotonergic Control of Gas-Trointestinal Development, Motility, and Inflammation. Comprehensive Physiology, 13, 4851-4868.
https://doi.org/10.1002/cphy.c220024
[17]  Jenkins, T., Nguyen, J., Polglaze, K. and Bertrand, P. (2016) Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8, Article 56.
https://doi.org/10.3390/nu8010056
[18]  Zhao, Z.-Q., Liu, X.-Y., Jeffry, J., Karunarathne, W.K.A., Li, J.-Q., Munanairi, A., et al. (2014) Descending Control of Itch Transmission by the Serotonergic System via 5-Ht1a-Facilitated GRP-GRPR Signaling. Neuron, 84, 821-834.
https://doi.org/10.1016/j.neuron.2014.10.003
[19]  Mishima, Y. and Ishihara, S. (2021) Enteric Microbiota-Mediated Serotonergic Signaling in Pathogenesis of Irritable Bowel Syndrome. International Journal of Molecular Sciences, 22, Article 10235.
https://doi.org/10.3390/ijms221910235
[20]  Gros, M., Gros, B., Mesonero, J.E. and Latorre, E. (2021) Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management. Journal of Clinical Medicine, 10, Article 3429.
https://doi.org/10.3390/jcm10153429
[21]  Holland, A.M., Bon-Frauches, A.C., Keszthelyi, D., Melotte, V. and Boesmans, W. (2021) The Enteric Nervous System in Gastrointestinal Disease Etiology. Cellular and Molecular Life Sciences, 78, 4713-4733.
https://doi.org/10.1007/s00018-021-03812-y
[22]  Wei, L., Singh, R. and Ghoshal, U.C. (2022) Enterochromaffin Cells—Gut Microbiota Crosstalk: Underpinning the Symptoms, Pathogenesis, and Pharmacotherapy in Disorders of Gut-Brain Interaction. Journal of Neurogastroenterology and Motility, 28, 357-375.
https://doi.org/10.5056/jnm22008
[23]  Yang, H., Chen, W.W., Zhu, R.K., Wang, J.F. and Meng, J.H. (2022) Critical Players and Therapeutic Targets in Chronic Itch. International Journal of Molecular Sciences, 23, Article 9935.
https://doi.org/10.3390/ijms23179935
[24]  Szöllősi, A.G., Oláh, A., Lisztes, E., Griger, Z. and Tóth, B.I. (2022) Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk. Frontiers in Pharmacology, 13, Article 745658.
https://doi.org/10.3389/fphar.2022.745658
[25]  Mahmoud, O., Soares, G.B. and Yosipovitch, G. (2022) Transient Receptor Potential Channels and Itch. International Journal of Molecular Sciences, 24, Article 420.
https://doi.org/10.3390/ijms24010420
[26]  Tian, B., Wang, X.-L., Huang, Y., Chen, L.-H., Cheng, R.-X., Zhou, F.-M., et al. (2016) Peripheral and Spinal 5-HT Receptors Participate in Cholestatic Itch and Antinociception Induced by Bile Duct Ligation in Rats. Scientific Reports, 6, Article No. 36286.
https://doi.org/10.1038/srep36286
[27]  Domocos, D., Selescu, T., Ceafalan, L.C., Iodi Carstens, M., Carstens, E. and Babes, A. (2020) Role of 5‐HT1A and 5‐HT3 Receptors in Serotonergic Activation of Sensory Neurons in Relation to Itch and Pain Behavior in the Rat. Journal of Neuroscience Research, 98, 1999-2017.
https://doi.org/10.1002/jnr.24633
[28]  Siiskonen, H. and Harvima, I. (2019) Mast Cells and Sensory Nerves Contribute to Neurogenic Inflammation and Pruritus in Chronic Skin Inflammation. Frontiers in Cellular Neuroscience, 13, Article 422.
https://doi.org/10.3389/fncel.2019.00422
[29]  Toyama, S., Tominaga, M. and Takamori, K. (2021) Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation. International Journal of Molecular Sciences, 22, Article 12365.
https://doi.org/10.3390/ijms222212365
[30]  Wan, M., Ding, L., Wang, D., Han, J. and Gao, P. (2020) Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases. Frontiers in Immunology, 11, Article 186.
https://doi.org/10.3389/fimmu.2020.00186
[31]  Bellono, N.W., Bayrer, J.R., Leitch, D.B., Castro, J., Zhang, C., O’Donnell, T.A., et al. (2017) Enterochromaffin Cells Are Gut Chemosensors That Couple to Sensory Neural Pathways. Cell, 170, 185-198.E16.
https://doi.org/10.1016/j.cell.2017.05.034
[32]  Dodds, K.N., Travis, L., Kyloh, M.A., Jones, L.A., Keating, D.J. and Spencer, N.J. (2022) The Gut-Brain Axis: Spatial Relationship between Spinal Afferent Nerves and 5-Ht-Containing Enterochromaffin Cells in Mucosa of Mouse Colon. American Journal of Physiology-Gastrointestinal and Liver Physiology, 322, G523-G533.
https://doi.org/10.1152/ajpgi.00019.2022
[33]  O’Mahony, S. (2006) Central Serotonergic and Noradrenergic Receptors in Functional Dyspepsia. World Journal of Gastroenterology, 12, 2681-2687.
https://doi.org/10.3748/wjg.v12.i17.2681
[34]  Qiao, L.Y. and Tiwari, N. (2020) Spinal Neuron-Glia-Immune Interaction in Cross-Organ Sensitization. American Journal of Physiology-Gastrointestinal and Liver Physiology, 319, G748-G760.
https://doi.org/10.1152/ajpgi.00323.2020
[35]  Verne, N.G., Himes, N.C., Robinson, M.E., Gopinath, K.S., Briggs, R.W., Crosson, B., et al. (2003) Central Representation of Visceral and Cutaneous Hypersensitivity in the Irritable Bowel Syndrome. Pain, 103, 99-110.
https://doi.org/10.1016/s0304-3959(02)00416-5
[36]  Merecz, K., Hirsa, M., Biniszewska, O., Fichna, J. and Tarasiuk, A. (2023) An Overview of 5-HT3 Receptor Antagonists as a Treatment Option for Irritable Bowel Syndrome with Diarrhea. Expert Opinion on Pharmacotherapy, 24, 1189-1198.
https://doi.org/10.1080/14656566.2023.2214314
[37]  Schwörer, H. and Ramadori, G. (1993) Treatment of Pruritus: A New Indication for Serotonin Type 3 Receptor Antagonists. The Clinical Investigator, 71, 659-662.
https://doi.org/10.1007/bf00184497
[38]  Chincholkar, M. (2020) Gabapentinoids: Pharmacokinetics, Pharmacodynamics and Considerations for Clinical Practice. British Journal of Pain, 14, 104-114.
https://doi.org/10.1177/2049463720912496
[39]  Sreekantaswamy, S.A., Mollanazar, N. and Butler, D.C. (2021) Gabapentinoids for Pruritus in Older Adults: A Narrative Review. Dermatology and Therapy, 11, 669-679.
https://doi.org/10.1007/s13555-021-00513-z
[40]  Bentham Science Publisher, B.S.P. (2013) Pharmacological Inhibition of Voltage-Gated Ca2+ Channels for Chronic Pain Relief. Current Neuropharmacology, 11, 606-620.
https://doi.org/10.2174/1570159x11311060005
[41]  Yamaguchi, T., Nagasawa, T., Satoh, M. and Kuraishi, Y. (1999) Itch-Associated Response Induced by Intradermal Serotonin through 5-HT2 Receptors in Mice. Neuroscience Research, 35, 77-83.
https://doi.org/10.1016/s0168-0102(99)00070-x
[42]  Dray, A. (1992) Mechanism of Action of Capsaicin-Like Molecules on Sensory Neurons. Life Sciences, 51, 1759-1765.
https://doi.org/10.1016/0024-3205(92)90045-q
[43]  Downs, A.M.R. and Kennedy, C.T.C. (1998) Successful Treatment of Intractable Palmoplantar Pruritus with Ondansetron. Archives of Dermatology, 134, 925-926.
https://doi.org/10.1001/archderm.134.8.925
[44]  Buey, B., Forcén, A., Grasa, L., Layunta, E., Mesonero, J.E. and Latorre, E. (2023) Gut Microbiota-Derived Short-Chain Fatty Acids: Novel Regulators of Intestinal Serotonin Transporter. Life, 13, Article 1085.
https://doi.org/10.3390/life13051085
[45]  Nzakizwanayo, J., Dedi, C., Standen, G., Macfarlane, W.M., Patel, B.A. and Jones, B.V. (2015) Escherichia Coli Nissle 1917 Enhances Bioavailability of Serotonin in Gut Tissues through Modulation of Synthesis and Clearance. Scientific Reports, 5, Article No. 17324.
https://doi.org/10.1038/srep17324
[46]  Bhattarai, Y., Muniz Pedrogo, D.A. and Kashyap, P.C. (2017) Irritable Bowel Syndrome: A Gut Microbiota-Related Disorder? American Journal of Physiology-Gastrointestinal and Liver Physiology, 312, G52-G62.
https://doi.org/10.1152/ajpgi.00338.2016
[47]  Kwon, Y.H., Wang, H.Q., Denou, E., Ghia, J., Rossi, L., Fontes, M.E., et al. (2019) Modulation of Gut Microbiota Composition by Serotonin Signaling Influences Intestinal Immune Response and Susceptibility to Colitis. Cellular and Molecular Gastroenterology and Hepatology, 7, 709-728.
https://doi.org/10.1016/j.jcmgh.2019.01.004
[48]  González Delgado, S., Garza-Veloz, I., Trejo-Vazquez, F. and Martinez-Fierro, M.L. (2022) Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease. International Journal of Molecular Sciences, 23, Article 15632.
https://doi.org/10.3390/ijms232415632
[49]  de Oliveira, C.S.F. and Tavaria, F.K. (2024) Therapeutic Textiles: A Promising Approach for Human Skin Dysbiosis? Experimental Dermatology, 33, e15081.
https://doi.org/10.1111/exd.15081
[50]  Azzimonti, B., Ballacchino, C., Zanetta, P., Cucci, M.A., Monge, C., Grattarola, M., et al. (2023) Microbiota, Oxidative Stress, and Skin Cancer: An Unexpected Triangle. Antioxidants, 12, Article 546.
https://doi.org/10.3390/antiox12030546
[51]  Sfriso, R., Egert, M., Gempeler, M., Voegeli, R. and Campiche, R. (2019) Revealing the Secret Life of Skin—with the Microbiome You Never Walk Alone. International Journal of Cosmetic Science, 42, 116-126.
https://doi.org/10.1111/ics.12594
[52]  Tate, D.E., Tanprasertsuk, J., Jones, R.B., Maughan, H., Chakrabarti, A., Khafipour, E., et al. (2024) A Randomized Controlled Trial to Evaluate the Impact of a Novel Probiotic and Nutraceutical Supplement on Pruritic Dermatitis and the Gut Microbiota in Privately Owned Dogs. Animals, 14, Article 453.
https://doi.org/10.3390/ani14030453
[53]  Badri, D., Jewell, D. and Panickar, K. (2019) Diet Intervention Alleviates Pruritus by Reducing Intestinal Inflammation to Improve Skin Health in Dogs (p09-001-19). Current Developments in Nutrition, 3, nzz033.P09-001-19.
https://doi.org/10.1093/cdn/nzz033.p09-001-19
[54]  Uchiyama, K., Naito, Y. and Takagi, T. (2019) Intestinal Microbiome as a Novel Therapeutic Target for Local and Systemic Inflammation. Pharmacology & Therapeutics, 199, 164-172.
https://doi.org/10.1016/j.pharmthera.2019.03.006
[55]  Foster, J.A., Rinaman, L. and Cryan, J.F. (2017) Stress & the Gut-Brain Axis: Regulation by the Microbiome. Neurobiology of Stress, 7, 124-136.
https://doi.org/10.1016/j.ynstr.2017.03.001
[56]  Long-Smith, C., O’Riordan, K.J., Clarke, G., Stanton, C., Dinan, T.G. and Cryan, J.F. (2020) Microbiota-Gut-Brain Axis: New Therapeutic Opportunities. Annual Review of Pharmacology and Toxicology, 60, 477-502.
https://doi.org/10.1146/annurev-pharmtox-010919-023628
[57]  Skonieczna-Żydecka, K., Marlicz, W., Misera, A., Koulaouzidis, A. and Łoniewski, I. (2018) Microbiome—the Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health. Journal of Clinical Medicine, 7, Article 521.
https://doi.org/10.3390/jcm7120521
[58]  Dong, X.T. and Dong, X.Z. (2018) Peripheral and Central Mechanisms of Itch. Neuron, 98, 482-494.
https://doi.org/10.1016/j.neuron.2018.03.023
[59]  Remröd, C., Lonne-Rahm, S. and Nordlind, K. (2007) Study of Substance P and Its Receptor Neurokinin-1 in Psoriasis and Their Relation to Chronic Stress and Pruritus. Archives of Dermatological Research, 299, 85-91.
https://doi.org/10.1007/s00403-007-0745-x
[60]  Roosterman, D., Goerge, T., Schneider, S.W., Bunnett, N.W. and Steinhoff, M. (2006) Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ. Physiological Reviews, 86, 1309-1379.
https://doi.org/10.1152/physrev.00026.2005
[61]  Lackner, J. (2008) Serotonin Receptor Modulators in the Treatment of Irritable Bowel Syndrome. Therapeutics and Clinical Risk Management, 4, 41-48.
https://doi.org/10.2147/tcrm.s140
[62]  Holtmann, G.J., Ford, A.C. and Talley, N.J. (2016) Pathophysiology of Irritable Bowel Syndrome. The Lancet Gastroenterology & Hepatology, 1, 133-146.
https://doi.org/10.1016/s2468-1253(16)30023-1
[63]  Pereira, M.P. and Ständer, S. (2017) Chronic Pruritus: Current and Emerging Treatment Options. Drugs, 77, 999-1007.
https://doi.org/10.1007/s40265-017-0746-9

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