Genetic study links sugar digestion defects to irritable bowel syndrome
Research carried out by a CIC bioGUNE team points to sucrose, among other sugars, as a key trigger of intestinal symptoms in individuals with a genetic predisposition to poor carbohydrate digestion, opening the door to personalised nutrition.
A new study by BRTA member CIC bioGUNE has uncovered a key genetic mechanism that increases the risk of irritable bowel syndrome (IBS) and worsens intestinal symptoms in people who carry defective copies of the saccharase-isomaltase (SI) gene. The research, published in Gastroenterology, suggests that sucrase may be a dietary trigger for genetically predisposed individuals, offering new insights that could shape future dietary recommendations and personalised treatments for irritable bowel syndrome.
Sucrase-isomaltase (SI) is an intestinal enzyme essential for the digestion of dietary carbohydrates, particularly sucrose and starch. Previous studies by the Gastrointestinal Genetics team at CIC bioGUNE and LUM University suggested a genetic link between SI enzyme defects and irritable bowel syndrome, whereby certain DNA changes cause reduced enzyme activity and inefficient digestion of carbohydrates, inducing symptoms such as bloating, diarrhoea and abdominal pain.
However, as the name suggests, SI is a special case in that it encompasses two enzymes with different carbohydrate-digesting properties (sucrase and isomaltase), both found in the SI protein encoded by a single gene. While previous research has associated genetic defects in IS with irritable bowel syndrome and responses to low-carbohydrate diets, it was unclear whether sucrase and isomaltase play distinct roles in disease risk and symptom severity.
In the new study, the Gastrointestinal Genetics team analysed genetic and health data from more than 360,000 individuals in the UK Biobank, and found that individuals with defective saccharase variants were at significantly increased risk of irritable bowel syndrome, while those with isomaltase defects were unaffected. At the same time, carriers defective in sucrase (but not isomaltase) experienced more severe gut symptoms and were more likely to avoid sucrose-rich foods. ‘In addition to maltose from starch (which is also digested by other enzymes), sucrase has the unique ability to break down sucrose,’ says lead study author Mauro D’Amato, professor of Medical Genetics at LUM University and Ikerbasque research professor at CIC bioGUNE ’It may be that this sugar triggers intestinal symptoms in individuals with genetic defects associated with reduced sucrase function. This not only contributes to understanding the risk of irritable bowel syndrome in people predisposed to poor carbohydrate digestion, but also supports the idea of tailoring their dietary treatment according to genetics,’ explains Mauro D’Amato.
Irritable bowel syndrome affects millions of people worldwide, often with unclear pathogenesis and limited treatment options. This study reinforces the importance of digestive enzyme genetics in the predisposition to irritable bowel syndrome and provides a rationale for dietary modifications, such as reducing sucrose intake, in genetically susceptible individuals. ‘While further studies are needed to validate these initial findings, our results have potential implications for the development of new diagnostic tools, dietary strategies and even enzyme-targeted therapies towards personalised approaches for the prevention and treatment of irritable bowel syndrome,’ adds Mauro D’Amato.
