gut health

HTR3A

The Impact of a Serotonin Receptor on IBS-D (HTR3A)

Written by Jasmine Foster, BSc, BEd on March 19th, 2020

HTR3A codes for a piece of the 5-HT3 serotonin receptor, which increases movement in the gut. Which genetic variants may predispose people to IBS? Find out here.

Serotonin and the Gut

Serotonin is best known as a neurotransmitter in the brain, and more specifically for its roles in mental health, reward, and happiness. However, serotonin plays myriad roles outside of the brain, as well, and it is essential for constriction and movement in the digestive system [R].

In the gut, serotonin regulates the secretion of mucus and pancreatic enzymes and the absorption of fluids. It also regulates the movement of muscles in the gut, which in turn determines how quickly food passes through the intestine [R, R].

Serotonin also plays a role in immune function and inflammation in the intestine. When serotonin is released into the gut, the secretion of inflammatory cytokines increases. Serotonin also increases the recruitment of white blood cells and platelets. Normally, this system helps kill pathogens and prevent them from crossing into the bloodstream; however, it can also lead to potentially dangerous inflammation [R, R].

In the gut, serotonin regulates inflammation, immunity, and the secretion of mucus and pancreatic enzymes.

What is HTR3A?

The HTR3A gene codes for a part of the 5-HT3 serotonin receptor. This is considered to be one of the three most important types of serotonin receptor in the gut (the others being 5-HT1b and 5-HT4) [R].

The 5-HT3 receptor is scientifically interesting because it has a different structure from all other types of serotonin receptor. When the 5-HT3 receptor is activated, it causes nausea, vomiting, and anxiety. Increased activation of these receptors also appears to predispose people to seizures [R, R, R, R].

These receptors are present throughout the nervous system, both inside and outside the brain. It is also found in non-neuronal cells, especially white blood cells [R].

The 5-HT3 Receptor and IBS

Given the importance of serotonin in the gut and the function of 5-HT3 in nausea and vomiting, it’s not surprising that this receptor is implicated in gut disorders like IBS.

Many IBS patients have abnormal serotonin systems. Specifically, people with IBS tend to secrete more serotonin, which results in increased movement of the gut tissues, increased inflammation, and more white blood cells in the intestine [R, R].

Some IBS medications block 5-HT3 receptors and prevent the action of serotonin in the gut. In this way, they reduce excess movement of gut muscles and slow down the rate at which food passes through the intestines [R].

However, 5-HT3 receptor blockers are only effective for some people with diarrhea-predominant IBS [R].

HTR3A codes for one of the parts of the 5-HT3 serotonin receptor, which causes nausea, vomiting, and increased gut motility when activated. 5-HT3 receptor blockers are effective for some cases of IBS-D.

HTR3A in People with IBS

In theory, variants in the 5-HT3 receptor that increase its activity could increase movement in the gut and increase susceptibility to IBS.

One variant in the HTR3A gene has been directly linked to IBS. At rs1062613, the minor ‘T’ allele was associated with increased rates of IBS and increased receptor activation [R, R].

Your HTR3A Results for IBS

SNP Table

variant	genotype	frequency	risk allele
rs1062613

SNP Summary and Table

HTR3A rs1062613

‘C’ = Normal HTR3A expression
‘T’ = Increased HTR3A expression, associated with increased rates of IBS
The ‘TT’ genotype is much more common in people of African descent (26%) compared to the global population (9.2%).

Recommendations

Lifestyle

Stress Reduction

Psychological stress is widely believed to trigger or worsen IBS. In fact, some researchers refer to both “irritable bowel” and “irritable brain” as equal factors in the development of IBS. Furthermore, anxiety and frustration with gut symptoms can further worsen these same symptoms. As such, many experts recommend stress management strategies as part of a holistic strategy to manage and treat this condition [R, R, R].

The precise relationship between 5-HT3 receptors and psychological stress hasn’t yet been fully unraveled in humans. However, in animals, blocking 5-HT3 receptors helps reduce depressive behavior and the sensation of pain [R, R, R, R].

Supplements

Herbal Supplements

A number of plant-derived compounds have been found to antagonize the 5-HT3 receptor. Many of these are currently under investigation for their potential to reduce chemotherapy-induced nausea and vomiting, but they may also be helpful in some cases of IBS [R].

Menthol, an active compound in peppermint, is among the herbal compounds found to block the 5HT3 receptor [R].

Peppermint is among the best-known and -studied natural remedies for IBS, and it has a significant chunk of evidence to back up its use. A meta-analysis of twelve studies and 835 patients found that peppermint oil reduced abdominal pain and other symptoms of IBS without adverse effects [R].

Other active compounds that block the 5-HT3 receptor include capsaicin (found in hot peppers), eugenol (found in cloves and holy basil), vanillin (found in vanilla), thujone (found in thyme and sage), cannabidiol (extracted from cannabis), and several compounds in ginger [R].

Of these, ginger, capsaicin, eugenol, and cannabidiol have also shown some potential in clinical studies of patients with IBS [R, R, R, R].

Many herbs contain compounds that can block the 5-HT3 receptor. The best-studied of these in IBS is peppermint.

Probiotics

One of the most likely causes of IBS is dysregulation of the gut flora. In fact, individuals with IBS often appear to have decreased diversity and numbers of beneficial microbiota and protective strains such as L. reuteri [R].

Fermented foods are a great way to increase your intake of diverse probiotic bacteria without the use of supplements. Consuming fermented milk products (which include buttermilk, cheese, yogurt, kefir, sour cream, and more) significantly improved symptoms of IBS in multiple clinical trials [R, R].

Another fermented food with promise for IBS is sauerkraut (a type of fermented cabbage) [R, R].

There is some laboratory evidence that acetate, which is produced by healthy gut flora, reduces the expression of the 5-HT3 receptor in intestinal tissues; this result suggests that certain acetate-producing probiotics may be helpful for those with problematic HTR3A variants. However, this has not yet been studied in humans [R].

Certain bacteria in the healthy gut flora may help suppress the expression of the 5-HT3 receptor in the gut.

Drugs

Some 5-HT3R receptor antagonists such as Alosetron and Cilansetron are available to treat diarrhea-predominant IBS. If you have severe IBS-D, your doctor may consider prescribing these medications. However, you should never take any medication without your doctor’s recommendation or prescription [R, R].

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More gut health blogs

Could This Gene Be Linked To Gut Inflammation? (ATG16L1) Could This Gene Play A Role In Inflammatory Bowel Disease? (STAT3) How Do Your Genes Respond to Dietary Fat? (TCF7L2) Do Your Genes Favor the Mediterranean Diet? (TCF7L2) How Does this Serotonin Receptor Affect Gut Inflammation? (HTR3E) The Impact of a Serotonin Receptor on IBS-D (HTR3A) How Can Neurotrophins Affect Gut Inflammation? (BDNF) Could Your IBS Symptoms Be Caused by an Enzyme Deficiency? (SI) What is the Connection Between β-Klotho and Gut Inflammation? (KLB) Can This Gene Worsen Gut Inflammation? (NOS2)

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Serotonin and the Gut What is HTR3A? Your HTR3A Results for IBS

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