Problems with IBS? Personalized solutions based on your genes

We tend to take happy bowels for granted — until something goes awry!  For many people, a daily battle seems to wage in their intestines.

Pain, discomfort, bloating, diarrhea and/or constipation…  a.k.a. IBS or irritable bowel syndrome.

There are multiple causes of IBS, and genetics can play a role in IBS symptoms. Pinpointing your cause can help you to figure out your solution.

Irritable Bowel Syndrome

IBS affects more than 10% of the population in Westernized countries [ref]

IBS is a functional GI disorder defined as having:

  • abdominal pain, bloating, gas
  • diarrhea (IBS-D)
  • constipation (IBS-C)
  • OR – a mix of diarrhea and constipation (IBS-M)

The diagnosis is often one of eliminating other conditions — such as celiac, Crohn’s, or ulcerative colitis — and thus being left with IBS.

The causes of IBS are often a mystery — both to the person who has it and to their doctor. The word ‘idiopathic’ gets used a lot.

According to the National Institute of Health “Doctors aren’t sure what causes IBS.”  Hmm…  not what someone with IBS wants to hear from their doctor! [source]

Often people will go through a series of dietary changes, trying to figure out which foods, if any, lead to their problems.

Researchers have come up with many theories about IBS.

I’m going to dig into a few of these theories and show how they link up to genetics. Then you can check your genetic data, and use that info to figure out the IBS solutions that may work best for you.

Digesting Carbs:

Carbs are supposed to be digested, broken down and absorbed, in the small intestines.  When that doesn’t happen — either due to lack of enzymes to break them down or increased gut motility — the carbs end up in the colon. Extra carbs in the colon feed the bacteria there, and they party all night, giving off gas.

While frank deficiencies of the enzymes that break down different carbohydrates are somewhat rare, researchers are now discovering that partial deficiencies could be causing IBS symptoms for some people.[ref]

Sucrase-isomaltase deficiency is a lack of the enzyme that breaks down the starches and sugars. SI deficiency leads to accumulation of unabsorbed carbs in the intestines. This leads to a change in the gut microbiome, increased short-chain fatty acids, increased gas, and often diarrhea, abdominal pain and bloating. [ref]

Lactose is a sugar found in milk and dairy products. Most people of European descent have inherited a genetic variant that still allows for the production of lactase as an adult. But for people who don’t produce lactase as an adult (e.g. most Asians, 10% of Caucasians), drinking milk may aggravate IBS symptoms.

Serotonin makes things move:

Most of the serotonin (5-hydroxytryptamine, 5-HT) your body produces is in the intestines. It acts both a neurotransmitter and immune system regulator. It is the signaling molecule that regulates motility, secretion, and vasodilation.  When the intestinal tract is stimulated, it produces more serotonin and more serotonin receptors.  [ref]

The microbes in the gut are able to influence the amount of serotonin synthesized there.[ref] So an overgrowth of certain bacteria could influence and increase serotonin synthesis. [ref]

There are several different serotonin receptors in the intestines. The overactivation of the 5-HT3R receptor has specifically been linked to IBS with diarrhea. One study showed that people with IBS-D had double the number of 5-HT3R in the intestinal mucosa, compared with a control group.[ref]

Bile acid synthesis:

Your body produces bile acids for digesting fats as well as for getting rid of waste products, such as bilirubin. Adults produce between 400 and 800 ml of bile per day.

Typically, the gallbladder stores bile when you haven’t recently eaten. Then it is released from the gallbladder into the upper part of the small intestines.  The bile acids then break up, or emulsify, fats so that they can be easily digested by lipases. [ref]

About 95% of the bile acids are reabsorbed when they reach the end of the small intestines.  They are recycled through the liver and then reused again.

If too much of the bile acid ends up in the colon, diarrhea will ensue…  This can be either from too much being produced or from not enough being reabsorbed at the end of the small intestines (at the ileum).

When excess bile acids reach the colon, they cause diarrhea by stimulating an increase in water in the stool.

Studies show that between 10 – 25% of patients with IBS-D had problems stemming from bile acids reaching the colon.[ref]

Enteric Nerve Irritation:

The nerves that cause peristalsis, or movement, in the intestines are called enteric nerves.  Several studies point to increased expression of TRPV1 in the enteric nerves of people with IBS. TRPV1 is a pain receptor and that also may play a role in the response to mechanical stimulation (i.e. foodstuff pressing on the intestines).

TRPV1 stands for transient receptor potential vanilloid type-1. It is also the receptor that capsaicin binds to, causing you to sense spicy heat. A study that looked at the TRPV1 receptors in biopsies from IBS patients found that they had a 3.5-fold increase compared to normal people. Basically, this causes hypersensitivity to pain in the intestines (irritability!). [ref]

Another study points to histamine as a possible cause of sensitized TRPV1 channels in IBS.[ref]  And to tie this back to bile acids, a study points to bile acids causing mast cells activation (releasing histamine) and increasing TRPV1 expression.[ref]

Variants in the TRPM8 gene have also been linked in large, genome-wide studies to increased risk of IBS-C. This transient receptor potential channel is also thought to be associated with bile acid secretion.  [ref]


Is IBS a genetic disorder?

Genetics plays a role in susceptibility to IBS. It is likely that for most people IBS is caused by a combo of several genetic susceptibility variants along with environmental (or diet) factors. [ref]

Carbohydrates Metabolism Genes:

SI gene:  The SI gene codes for the enzyme sucrase-isomaltase, which metabolizes starches and sugars for absorption in the intestines. The rs9290264 variant is fairly common and about 30% of the population carries it. It is linked to a  decrease in enzyme activity and an increased risk of IBS-D (diarrhea subtype) and IBS-M (mixed diarrhea/constipation).

Even in people who don’t have IBS, the rs9290264 variant was associated with more frequent pooping. (Yes, there were 133 subjects who recorded their daily defecation patterns.)[ref]

Check your genetic data for rs9290264 (23andMe v4, v5; AncestryDNA)

  • C/C: normal
  • A/C: somewhat reduced enzyme activity, increased risk of IBS-D and IBS-M
  • A/A: reduced enzyme activity, 3.8x increased risk of IBS-D and IBS-M, increased daily defecation [ref][ref]

 

Lactose: This genetic variant will indicate whether you are likely to still produce lactase as an adult.

Check your genetic data for rs4988235 (23andMe v.4, v.5; AncestryDNA):

  • A/A: Still produces lactase as an adult
  • A/G: Still produces lactase as an adult, but less than those with A/A [ref]
  • G/G: No longer produces lactase as an adult

Serotonin genetic variants:

HTR3E gene: This gene codes a subunit of the 5-hydroxytryptamine receptor (serotonin receptor). It is mainly expressed in the gastrointestinal tract.

Check your genetic data for rs56109847 (23andMe v4, AncestryDNA):

  • G/G: normal
  • A/G: increased risk of IBS-D
  • A/A: 4 to 8 fold increased risk of IBS D[ref][ref]

Note that this SNP used to be called rs62625044 and may be referred to in studies as 76G>A.

HTR3A gene: This gene codes a subunit of the 5-hydroxytryptamine receptor (serotonin receptor).

Check your genetic data for rs1062613 (23andMe v4, v5; AncestryDNA):

  • T/T: increased risk of IBS-D, increased serotonin receptor function, increased risk of dyspepsia [ref][ref][ref]
  • C/T: somewhat increased risk of IBS-D, increased serotonin receptor function
  • C/C: normal

 

Bile acid synthesis:

KLB gene: The klotho-B gene is involved in the regulation of bile acid synthesis.[ref]

Check your genetic data for rs17618244 (AncestryDNA only):

  • AA: normal transit time
  • AG: normal transit time
  • GG: (most common genotype) faster colonic transit time in IBS-D[ref]

Enteric nervous system:

There are several TRPV1 variants that have been studied in regards to people’s response to spicy foods (capsaicin). While none of these variants have been researched in relation to IBS, it would make sense that overexpression of TRPV1 genetically would increase the risk of IBS. Check your spicy food genes here. 

The TRPM8 gene has also been implicated in the risk for IBS-Mixed and IBS-C.

Check your genetic data for rs10166942 (23andMe v4, v5; AncestryDNA):

  • C/C: increased risk of IBS-C, slower colonic transit time [ref]
  • C/T: increased risk of IBS-C, slower colonic transit time
  • T/T: normal

 


Lifehacks:

Carbohydrates and Enzymes:

If you carry the SI genetic variant that increases the risk of IBS-D, cutting down on the consumption of starches and sucrose is an obvious first step. If you don’t want to cut out carbs altogether, try spacing out your starch/sugar consumption throughout the day. Don’t overwhelm your intestines with a big meal of starches and sugars.  In particular, researchers found that limiting starches, which are converted to maltose, was important.[ref]

There are digestive enzymes available that contain sucrase and maltase. Klaire Labs Vital-Zymes contains both sucrase and maltase and is available on Amazon.

TRP channels (enteric nervous system):

The probiotic VSL#3 has been shown in animals to decrease the number of mast cells (histamine releasers) in the colon and to decrease TRPV1 expression.[ref]  VSL#3 is available online or at your local health food store. It is expensive, but a lot of people swear by it.

Peppermint, which helps some people with IBS symptoms, activates TRPM8.  If you carry the TRPM8 variant (above) – or even if you don’t – give peppermint essential oil or peppermint tea a shot.

Avoiding spicy foods may also help. Capsaicin, which causes the spiciness in hot peppers, can be used to test for hypersensitivity of the TRPV1 channel.  This is done by swallowing a capsule with .75mg of capsaicin and seeing how much symptoms worsen.[ref]

Cannabinoids:

A prescription cannabinoid receptor agonist, dronabinol, has been shown to slow down colonic motility in IBS-D and IBS-Mixed patients.[ref] Currently, dronabinol is only approved by the FDA for chemotherapy and HIV/AIDS patients. If you live in a state where THC is legal, it might be something to consider.

CBD oil binds to the TRPV1 receptor at certain doses. Read more about CBD and your genes.

Diets to try:

Just do a quick google search for more information on any of these that you haven’t heard of before.

Gluten-free:
The symptoms of gluten intolerance often overlap with IBS. Eliminate gluten-containing foods for a week or two and see if it helps. Then add back in the gluten-containing foods…  see if it makes IBS come back.

FODMAPS:
A diet that eliminates many of poorly absorbed and easily fermentable foods that your colon bacteria like to munch on (producing gas and painful bloating).

Carnivore:
While somewhat extreme sounding, a diet of eating only animal foods (meat, dairy, eggs) is purported by some to cure IBS. It makes sense, in a way, because it would eliminate most fiber that bacteria could eat, thus reducing the painful bloating and gas.

Avoiding Nickel:
People with nickel allergy can be sensitive to foods that contain nickel.  These foods include cocoa, tomatoes, wheat, corn, onions, shellfish, and more[ref]

Low-histamine diet:
This diet reduces histamines in the intestines by eliminating foods high in histamine such as wine, fermented foods, aged meats and cheeses, tomatoes, spinach, chocolate, etc.



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2 Comments on “Problems with IBS? Personalized solutions based on your genes

  1. I am really interested in the HTR3E gene, is there a way to test for that on version 5 of 23 and me?

    • That specific location on the gene isn’t covered in the v5 data from 23andme.
      There is a new study out on IBS-D (cites the study referenced for HTR3E) that you might be interested in reading: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434247/ In a nutshell, the samples from IBS-D patients had much, much higher expression of the serotonin receptors than normal people. And a symptom of excess serotonin is diarrhea.
      Tryptophan is the amino acid needed to make serotonin. If you are up for experimenting, you could try a diet low in tryptophan for a couple of days. Keep in mind that serotonin is also a neurotransmitter involved in mood, so you may not want to experiment with that if you have problems with mood disorders.
      Debbie

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