Sucrase-isomaltase (SI), a crucial intestinal enzyme for the digestion of dietary carbohydrates, including sucrose and starch, has been closely studied by the Gastrointestinal Genetics team at CIC bioGUNE – BRTA and LUM University. Their previous research highlighted a genetic connection between SI deficiencies and Irritable Bowel Syndrome (IBS), pinpointing specific DNA alterations resulting in diminished enzymatic activity and inefficient carbohydrate digestion. These genetic irregularities often trigger symptoms such as bloating, diarrhoea, and abdominal pain. The SI enzyme is unique because it comprises two distinct enzymes—sucrase and isomaltase—both components of the SI protein encoded by a single gene. Although earlier studies established a link between SI genetic abnormalities and IBS, along with reactions to low-carbohydrate diets, the distinct roles of sucrase and isomaltase in disease risk and symptom intensity remained unclear.
Building upon their prior work, the Gastrointestinal Genetics team conducted a new investigation, analysing genetic and health data from over 360,000 individuals registered in the UK Biobank. Their findings revealed that individuals carrying defective variants of sucrase were significantly more prone to IBS, whereas those with isomaltase defects showed no increase in risk. Importantly, those with sucrase deficiencies not only faced a higher risk of IBS but also suffered more severe bowel symptoms and tended to avoid foods rich in sucrose. “On top of digesting maltose from starch, which other enzymes also process, sucrase uniquely breaks down sucrose,” explained Mauro D’Amato, Professor of Medical Genetics at LUM University and Ikerbasque Research Professor at CIC bioGUNE. He noted that sucrose might trigger bowel symptoms in those with genetic mutations that reduce sucrase function. This insight is crucial for understanding IBS risk in individuals predisposed to carbohydrate maldigestion and supports the notion of customising their dietary treatment based on their genetic profile.
IBS, affecting millions globally, often presents with ambiguous causes and limited treatment options. This latest study underscores the significance of digestive enzyme genetics in predisposing individuals to IBS. It offers a rationale for dietary modifications, such as reducing sucrose intake, in those genetically susceptible. “While further research is necessary to confirm these preliminary findings,” added Mauro D’Amato, “our results hold potential implications for the development of novel diagnostic tools, dietary strategies, and even enzyme-targeted therapies aimed at personalised approaches to preventing and treating IBS.” This progressive understanding could lead to more targeted, effective management strategies that enhance the quality of life for those affected by IBS.
More information: Mauro D’Amato et al, Domain-Specific Effects of Sucrase-Isomaltase Genotype in Irritable Bowel Syndrome, Gastroenterology. DOI: 10.1053/j.gastro.2025.01.242
Journal information: Gastroenterology Provided by CIC bioGUNE
