Irritable Bowel Syndrome


Irritable Bowel Syndrome

Our IBS panel tests for 4 bio-markers (histamine, tryptophan, serotonin and GABA). The levels of these substances in the stool give us valuable information on how to treat the complex picture of IBS.

IBS vs IBD what’s the difference?

Irritable bowel syndrome (IBS) and Irritable bowel disease (IBD) are distinct conditions with different mechanisms and causes. They share symptoms like abdominal pain and altered bowel habits, making clinical differentiation challenging. However, their underlying pathology sets them apart. IBS involves functional bowel disorders without inflammation or structural abnormalities. On the other hand, IBD includes chronic inflammatory diseases, such as Crohn's disease and ulcerative colitis, characterized by intestinal mucosa inflammation (1) (2). The underlying cause of IBS involves factors like altered gut motility, visceral hypersensitivity, and abnormal gut-brain interactions. Dysregulation of the gut-brain axis and abnormal immune responses play a role (3) (4). IBD, in contrast, involves a dysregulated immune response resulting in chronic gastrointestinal tract inflammation. Genetic factors, environmental triggers, and abnormal immune responses contribute to its development. Treatment approaches vary for IBS and IBD due to their different causes. Assessing these underlying conditions is crucial for accurate diagnosis and targeted therapies.

Summary Table:

IBS Table

Irritable bowel syndrome (IBS)


For a long time, irritable bowel syndrome was only associated with a bowel problem. But new research has shown that it is also a disorder of the gut-brain axis. We are all familiar with the gut-brain connection: when we are very upset or anxious, we feel nauseous and have a queasy feeling in our stomach. This is often heightened in people with IBS. The gut and brain communicate through the gut-brain axis via microbiota, hormones, neurotransmitters, and sensory neurons. Our IBS panel tests for 4 of these messengers (histamine, tryptophan, serotonin and GABA). The levels of these substances in the stool give us valuable information on how to treat the complex picture of IBS. As IBS is a multifactorial disease, it is also useful to rule out dysbiosis, candida overgrowth, parasites, true food allergies and leaky gut. These are often contributing factors in IBS.

Histamine, a key regulator of bodily functions, can lead to adverse effects, including allergies and intolerance, particularly for those with irritable bowel syndrome (IBS), histamine intolerance (HIT), allergy, asthma and hay fever. In IBS, histamine exacerbates symptoms, influencing enteral nerves, stress, sleep disorders and inflammation (5). Elevated histamine levels in the gut result from various sources, including certain foods, medications, bacteria and mast cell degranulation, often triggered by mechanical stimuli like bloating. HIT, often due to Diamine oxidase DAO deficiency or imbalance, manifests with symptoms like headaches, tachycardia, gastrointestinal problems, hypotension and joint pain, affecting approximately 1% of the population. DAO breaks down histamine in various organs, but factors like inflammatory bowel disease, alcohol, drugs and painkillers can inhibit it, causing histamine-related issues (6). There's also a hormonal link between elevated estrogen levels and histamine release. If the levels in the gut rise, symptoms similar to an allergy appear such as diarrhoea, pain, nausea vomiting, itchy skin, which can go as far as shortness of breath and bradycardia (7) (8). As well as that it can lead to increased levels of stress, which leads to difficulties in falling asleep and sleeping through (9). Histamine also contributes to an increase gut permeability (10) of the gut mucosa and therefore contributes to leaky gut syndrome.

Serotonin levels in the intestine influence peristalsis, nausea and pain sensation (11). Altered serotonin levels can lead to diarrhea (12) (13)or constipation (14) (15) and a quick change between them in irritable bowel syndrome patients. Sensitization and desensitization of enteric nerves may contribute to the mixed irritable bowel syndrome (16). Serotonin levels can be affected due to genetic or environmental factors, but more often due to environmental factors e.g. dysbiosis, diet, supplementation, drugs and toxins.

Tryptophan, a vital amino acid, plays a crucial role in supporting a healthy intestinal barrier (17), exhibiting anti-inflammatory effects (18), enhancing mental health, and improving sleep quality (19) (20). Derived mainly from dietary protein, it contributes to the production of proteins that fortify the intestinal barrier such as sIgA, β-defensins and tight junction proteins (17). Tryptophan also activates the mTOR signalling system, promoting regeneration and repair (17) of the intestinal epithelium. In the large intestine, it generates anti-inflammatory indole compounds and kynurenic acid, known for its antioxidant and neuroprotective properties. Tryptophan is essential for serotonin synthesis, vital for mood regulation, and contributes to melatonin production, improving sleep quality. While dietary sources provide most tryptophan, certain bacteria and probiotics can enhance its availability. Fructose malabsorption can impact tryptophan absorption, emphasizing the importance of addressing such conditions for maintaining a healthy tryptophan balance in the body.

GABA, the primary inhibitory neurotransmitter in the nervous system, plays a crucial role in alleviating irritable bowel pain through the gut-brain axis. Produced by intestinal bacteria, GABA regulates anxiety, stress, circadian rhythm, and sleep (21). In addition, GABA helps with improving memory and mood and influences our pain perception (22). It inhibits the transmission of pain signals from the intestine to the brain and activates nociceptor suppression in the enteric nervous system. However, GABA's analgesic effect is dependent on optimal pH levels (23) between 5.3 and 6.2, emphasizing the importance of maintaining an acidic intestinal pH for effective relief of irritable bowel pain.


1. Camilleri, M., & Ford, A. C. (2012). Irritable bowel syndrome: Pathophysiology and current therapeutic approaches. Handbook of Experimental Pharmacology, 217, 99–113.

2. Barbara, G., Feinle-Bisset, C., & Ghoshal, U. C. (2016). The Intestinal Microenvironment and Functional Gastrointestinal Disorders. Gastroenterology, 150(6), 1305–1318.

3. Neurath, M. F. (2019). Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nature Immunology, 20(8), 970–979.

4. de Souza, H. S. P. (2020). Etiopathogenesis of inflammatory bowel disease: today and tomorrow. Current Opinion in Gastroenterology, 36(4), 290–297.

5. Smolinska, S et al. (2014). Histamine and gut mucosal immune regulation. Allergy, 69(3), 273–281.

6. Kovacova-Hanuskova E, Buday T, Gavliakova S, Plevkova J. Histamine, histamine intoxication and intolerance. Allergol Immunopathol (Madr). 2015;43(5):498-506. doi:10.1016/j.aller.2015.05.001

7. Ganesh, B. P., et al. (2018) Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes Protein Kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium (2018). Mucosal Immunol PMC 2018 January 26.

8. Ding, F. C. L. et al. (2019). Probiotics for paediatric functional abdominal pain disorders: A rapid review. Paediatrics and Child Health (Canada), 24(6), 383–394.

9. Thakkar MM. Histamine in the regulation of wakefulness. Sleep Med Rev. 2011 Feb;15(1):65-74. doi: 10.1016/j.smrv.2010.06.004. Epub 2010 Sep 20. PMID: 20851648; PMCID: PMC3016451.

10. Chen M, Ruan G, Chen L, Ying S, Li G, Xu F, Xiao Z, Tian Y, Lv L, Ping Y, Cheng Y, Wei Y. Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome. Front Endocrinol (Lausanne). 2022 Feb 16;13:817100. doi: 10.3389/fendo.2022.817100. PMID: 35250873; PMCID: PMC8888441.

11. Ranuh R et al. (2019) Effect of the probiotic Lactobacillus plantarum IS-10506 on BDNF and 5HT stimulation: role of intestinal microbiota on the gut-brain axis. Iran J Microbiology; Volume 11 Number 2 (April 2019) 145-150

12. Dunlop, S. P. et al. (2005). Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clinical Gastroenterology and Hepatology, 3(4), 349–357.

13. Yu, F., Huang et al. (2016). Comparison of 5-hydroxytryptophan signalling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis, 22(12), 3451–3459.

14. Riezzo G (2019). Effects of long-term administration of Lactobacillus reuteri DSM-17938 on circulating levels of 5-HT and BDNF in adults with functional constipation. Benef Microbes. 2019 Mar 13;10(2):137-147. doi: 10.3920/BM2018.0050. Epub 2018 Dec 21.

15. Mezzasalma V et al. (2016) The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation. 2016. doi:10.1155/2016/4740907

16. Horii Y et al. (2015): The serotonin receptor mediates changes in autonomic neurotransmission and gastrointestinal transit induced by heat-killed Lactobacillus brevis SBC8803. Benef Microbes. 2015;6(6):817-22. doi: 10.3920/BM2015.0031. Epub 2015 Aug 11.

17. Liang, H. et al. (2019). Dietary L-tryptophan supplementation enhances the intestinal mucosal barrier function in weaned piglets: Implication of tryptophan-metabolizing microbiota. International Journal of Molecular Sciences, 20(1), 1–13.

18. Zelante et al. (2013). Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity, 39(2), 372–385.

19. Chong HX et al. (2019): Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomised, double-blind, placebo-controlled study. Benef Microbes. 2019 Apr 19;10(4):355-373

20. Rudzki, L. et al. (2019) Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study. Psychoneuroendocrinology, 100, 213–222.

21. Icenhour A et al. (2019) Elucidating the putative link between prefrontal neurotransmission , functional connectivity , and affective symptoms in irritable bowel syndrome. Sci Rep. 2019;(August):1-11. doi:10.1038/s41598-019-50024-3

22. Loeza-Alcocer, E. et al. (2019). Peripheral GABA receptors regulate colonic afferent excitability and visceral nociception. Journal of Physiology, 597(13), 3425–3439.

23. Thwaites DT, Basterfield L, McCleave PM, Carter SM, Simmons NL. Gamma-Aminobutyric acid (GABA) transport across human intestinal epithelial (Caco-2) cell monolayers. Br J Pharmacol. 2000 Feb;129(3):457-64. doi: 10.1038/sj.bjp.0703069. PMID: 10711343; PMCID: PMC1571855.