Irritable Bowel Syndrome: An Explanation That’s Not So Irritating

31. January 2017

The symptoms of IBS can have a serious impact on the daily lives of those affected. The diagnosis "functional disorder for which there is no organic cause" is unsatisfying. Researchers have now discovered a genetic defect that can explain many symptoms.

The enzyme sucrase-isomaltase is essential for the digestion of carbohydrates in the human intestine. Genetic variation of the enzyme could, according to a recent study by the Karolinska Institute in Stockholm, be a possible cause of irritable bowel syndrome and would explain why some patients feel better when they eat low carb.

Three different types of irritable bowel

Irritable bowel syndrome is widespread. In Western countries 10 to 20 percent of the population suffer from this form of gastrointestinal ailment. According to estimates, IBS patients make up as much as 50 percent of any gastroenterologist’s patient appointments. Typical characteristics include pain or discomfort in the abdomen, along with a change in stool frequency and consistency. Patients with irritable bowel syndrome can be divided into three groups:

  1. Patients who frequently suffer diarrhoea.
  2. Patients who frequently suffer constipation.
  3. Patients with alternating stool consistency.

Irritable bowel syndrome: a diagnosis based on exclusion

The diagnosis “irritable bowel syndrome” is in a strict sense a diagnosis created by exclusion. It arises if, despite cautious examination of the patient, no organic cause for existing abdominal complaints can be found. Therefore, irritable bowel syndrome is referred to as a “functional disease”. For doctors and patients equally this diagnosis is often unsatisfactory.

The suspected triggers of the ailment, aside from food intolerances, stress and dysbioses of the intestinal flora, include genetic factors. One such genetic variant exists for the gene which codes for the enzyme sucrase-isomaltase.

Sucrase-isomaltase degrades polysaccharides

The human body produces this enzyme in the small intestine and to a lesser extent on the surface of microvilli in the colon. There it is responsible for breaking down polysaccharides. In very rare instances both gene copies fail on account of a congenital autosomal recessive fault. Far more often gene variants occur that code for an enzyme with reduced enzymatic capacity. “Mutations in the gene for sucrase-isomaltase are often found with inherited types of sucrose intolerance”, Mauro D’Amato from Karolinska Institute in Stockholm says.

If sucrase-isomaltase no longer functions to its full capacity, sucrose intolerance occurs. The sufferers’ digestive system might then only break down sucrose to a limited extent. The excess polysaccharides ferment in the human body, which can lead to abdominal cramps, diarrhoea and vomiting – the same symptoms which irritable bowel syndrome patients with frequent diarrhoea experience.

“People with irritable bowel syndrome often experience their symptoms in association with certain foods, especially in combination with fermentable carbohydrates”, D’Amato says. “We tested the hypothesis that genetic changes related to breaking down disaccharides – simple carbohydrates from sugars and starch – are associated with an increased risk of irritable bowel syndrome”.


Study leader Mauro D`Amato © Mauro D`Amato

Enzyme variant loses 35% of its working capacity

The scientists led by Mauro D’Amato searched for these genetic alterations in seven symptomatic individuals from four different families. In doing so they sequenced the sucrase-isomaltase gene of those affected and found different genetic variants of the gene. With one of these variants the amino acid valine is replaced by phenylalanine in the enzyme. When the scientists examined both enzyme variants in a cell model in vitro, it was found that the phenylalanine variant had a 35 percent reduced enzymatic capacity in comparison to the valine-variant.

“The significant loss of enzyme activity of the sucrase-isomaltase coincides with poor carbohydrate digestion in the gut and may lead to malabsorption and to abdominal discomfort”, co-senior author Hassan Naim of the Veterinary Medicine University of Hannover (Germany) says.

Irritable bowel patients carry the 15Phe variant twice as often as healthy individuals do

Data from a cohort study involving 1,887 volunteers from Sweden, Italy and the USA shows: patients with irritable bowel syndrome carry the 15Phe variant in their genome twice as often as do healthy control patients. The 15Phe variant was also associated with a lack of specific intestinal bacteria (Parabacteroides), indicating that intestinal flora has a role in the symptoms.

“Although there is probably no causal relationship between these two phenomena, the negative correlation of the 15Phe allele with the presence of Parabacteroides could help in the identification of patients with irritable bowel syndrome and defective sucrase-isomaltase”, the scientists write.

FODMAP could be individualised

Many irritable bowel patients, especially patients in the diarrhoea-group, benefit from a so-called FODMAP-restricted diet. FODMAP stands for “fermentable oligosaccharides, disaccharides and monosaccharides as polyols” and refers to a group of short-chain carbohydrates and polyvalent alcohols which occur in many foods and induce symptoms in some patients with an irritable bowel. “By knowing the sucrose-isomaltase status of a patient, this diet allows the needs of patients to be more precisely defined”, says Mauro D’Amato.


Gut feeling of sufferers seems right

What the researchers were able to show in their study had already apparently been suspected by the majority of sufferers for some time: 52 percent of 1,242 US patients who had filled out the “irritable bowel syndrome” questionnaire in 2007, provided this answer when asked for the presumed reason for their complaints: irritable bowel syndrome is caused by a deficiency of digestive enzymes.



Functional variants in the sucrose – isomaltase gene associate with increased risk of irritable bowel syndrome

4 rating(s) (4.5 ø)


Dr. med. Mohamed Shehab
Dr. med. Mohamed Shehab

nice and valuable presentation

#2 |
Marion Zerbst
Marion Zerbst

I suffered from this since my childhood (frequent diarrhea, abdominal cramps, flatulence) and found that an Ayurvedic herbal remedy called Triphala, which is used for the treatment of digestive problems, helped me surprisingly well. No diarrhea, no painful flatulence any more. Heard from a lot of other people who cured their digestive problems with this as well. Maybe doctors should try it with their patients. Tolerability is very good, no side effects.

#1 |

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