How Serotonin Level Fluctuation Affects the Effectiveness of Treatment in Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is one of the most commonly diagnosed functional gastrointestinal (GI) disorders. It affects both men and women. Enteric serotonin (5HT) is responsible for gut motility, secretion, visceral hypersensitivity, and inflammation. The serotonin reuptake transporter (SERT) maintains serotonin levels by regulating its reuptake. An increase in SERT expression causes a decrease in serotonin, which leads to IBS-C (irritable bowel syndrome, constipation-predominant), whereas a decrease in SERT transcription causes an increase in serotonin, which leads to IBS-D (irritable bowel syndrome, diarrhea-predominant). Some factors can alter SERT transcription, such as certain bacteria, inflammation, growth factor, and glucagon-like peptide-1. This shows that 5HT and SERT both have an important role in IBS pathophysiology so that it would be a better subject to target for the treatment aspect of IBS. 5HT3 receptor antagonists are advisable for IBS-D to block the excessive activity of serotonin at the 5HT3 receptor and reduce gut motility. For IBS-C, we prescribe 5HT4 receptor agonists, which promote gut motility. Also, the latest treatment approach, antidepressant drugs TCAs (tricyclic antidepressants) and SSRIs (selective serotonin reuptake inhibitors), are helpful by modulating serotonin levels in the gut. In this literature review, we found that serotonin is one of the main pathophysiological factors for IBS, and we can treat IBS by targeting serotonin function on gut motility.

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

“…IBS-D patients show significantly elevated serotonin levels in blood and urine compared with controls and IBS-C patients [ 51 ]. However, high serotonin levels do not seem to be specific to an IBS subtype, as other studies have detected increased 5-HT concentrations in both IBS-C and IBS-D patients [ 52 ]. IBS patients show lower concentrations of the main 5-HT metabolite, 5-HIAA (5-hydroxyindole acetic acid), and a lower 5-HIAA/5-HT ratio [ 46 ], although hypersensitive IBS patients show increased concentrations of 5-HIAA compared with non-hypersensitive ones [ 53 ].…”

Investigation the effectiveness of duloxetine in quality of life and symptoms of patients with irritable bowel syndrome

“…SSRIs revealed different results and have been discontinued in most cases due to their sexual side effects. [ 13 14 15 ] For example, it has been shown that citalopram has no superiority over placebo in controlling IBS symptoms. [ 20 ]…”

“…Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), which has been approved in the United States and Europe for the treatment of the major depressive disorder, generalized anxiety disorder, peripheral neuropathy in patients with diabetes and fibromyalgia, but it has not been approved for the treatment of irritable bowel syndrome. [ 13 14 ] In an open-label study on the duloxetine impact on symptoms of irritable bowel syndrome, duloxetine resulted in significant improvement in the severity of pain, the severity of illness, quality of life, anxiety, and disability at work and life, but this study was conducted on small sample size. [ 15 ] Considering the high prevalence of irritable bowel syndrome and its functional disorder associated with considerable costs for the individual and health system, paying attention to its treatment is crucially important.…”

The Ketogenic Diet Improves Gut–Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems

“…These molecules have become attractive targets for pharmacological treatments to reduce or promote gut motility, specifically for the IBS-D and IBS-C subtypes [15]. Furthermore, diets fortified with natural compounds (such as berberine or resveratrol) have been recently proposed as a therapeutic intervention to reduce serotonin signaling in IBS patients [16][17][18] and animal models [3].…”