2025/02/17

Genetic study links defects in sugar digestion to irritable bowel syndrome

Sucrase-isomaltase (SI) is an intestinal enzyme essential for the digestion of dietary carbohydrates, particularly sucrose and starch.

Research highlights sucrose as a key trigger of bowel symptoms in individuals with a genetic predisposition to carbohydrate maldigestion, paving the way for personalized nutrition.

A recent study, published in Gastroenterology, has uncovered a genetic mechanism that increases the risk of irritable bowel syndrome (IBS) and exacerbates bowel symptoms in individuals with defective copies of the SI gene. This finding offers new perspectives for future dietary recommendations and personalized treatments for IBS.

A new study has uncovered a key genetic mechanism that increases the risk of irritable bowel syndrome (IBS) and worsens bowel symptoms in individuals who carry defective copies of the sucrase-isomaltase (SI) gene. The research, published in Gastroenterology, suggests sucrose may be an alimentary trigger for genetically predisposed individuals, offering new insights that could shape future dietary recommendations and personalized treatments in IBS.

Sucrase-isomaltase (SI) is an intestinal enzyme critical for the digestion of dietary carbohydrates, particularly sucrose and starch. Previous studies from the Gastrointestinal Genetics team at CIC bioGUNE, member of BRTA, and LUM University suggested a genetic link between SI defects and IBS, whereby certain DNA changes cause reduced enzymatic activity and inefficient digestion of carbohydrates, thus inducing symptoms like bloating, diarrhoea, and abdominal pain. As the name gives away, however, SI is a special case in that it encompasses two enzymes with different carbohydrate-digesting properties (sucrase and isomaltase), both found on the SI protein encoded by a single gene. While earlier research associated SI genetic defects with IBS and responses to low-carb 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 now analysed genetic and health data from over 360.000 individuals in the UK Biobank and found that individuals with defective sucrase variants were exposed to a significantly higher risk of IBS, while those with isomaltase defects were not affected. At the same time, sucrase (but not isomaltase) defective carriers experienced more severe bowel symptoms, and were more likely to avoid sucrose-rich foods. “On top of maltose from starch (which is also digested by other enzymes), sucrase has the unique ability to break down sucrose” said senior author Mauro D’Amato, Ikerbasque Research Professor at CIC bioGUNE and Professor of Medical Genetics at LUM University, “and it may be so that this sugar triggers bowel symptoms in individuals with genetic defects associated with reduced sucrase function. This not only contributes to understanding IBS risk in people predisposed to carbohydrate maldigestion but also supports the idea of tailoring their dietary treatment based on genetics.”

IBS affects millions worldwide, often with unclear pathogenesis and limited treatment options. This study reinforces the importance of digestive enzyme genetics in IBS predisposition and provides rationale for dietary modifications - such as reducing sucrose intake - in genetically susceptible individuals. “While further studies are needed to validate these initial findings”, added Mauro D’Amato, “our results may have implications for the development of novel diagnostic tools, dietary strategies, and enzyme-targeted therapies towards personalized approaches to IBS prevention and treatment”.

The study involved researchers from Spain (CIC bioGUNE), Italy (LUM University and University of Naples) and Germany (University of Veterinary Medicine Hannover), and received funding from the Spanish Government MCIN/AEI/10.13039/501100011033 (PCI2021-122064-2A) and the German Federal Ministry for Education and Research BMBF (01EA2208B) under the umbrella of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund ERA-HDHL (GA N° 696295 of the EU Horizon 2020 Research and Innovation Programme).

Reference: Torices L, Bonfiglio F, Esteban-Blanco C, Zamfir-Taranu A, Naim HY, D’Amato M. Domain-specific effects of sucrase-isomaltase genotype in irritable bowel syndrome. Gastroenterology. DOI: 10.1053/j.gastro.2025.01.242.

About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.

About BRTA
BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

Spanish version