New study reveals genetic defects in carbohydrate digestion influence diet response in patients with irritable bowel syndrome 

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Irritable bowel syndrome (IBS) affects up to 10% of the global population and remains challenging to treat due to the wide variation in patient symptoms and responses to dietary or pharmacological interventions.

An international study, recently published in Clinical Gastroenterology & Hepatology involving researchers from the Institute of Clinical Molecular Biology (IKMB) in Kiel, now shows higher efficacy of dietary interventions in IBS patients with genetic defects in carbohydrate digestion.

The research could lead to tailored IBS treatments, using genetic markers to predict which patients benefit from specific dietary interventions.

Irritable bowel syndrome (IBS) is a digestive disorder affecting up to 10% of the global population, characterized by abdominal pain, bloating, diarrhea, or constipation. Despite its prevalence, treating IBS remains a challenge as symptoms and responses to dietary or pharmacological interventions vary significantly.

Patients often connect their symptoms to the consumption of certain foods, especially carbohydrates, and their dietary elimination or reduction has emerged as an effective treatment option, though not all patients experience the same benefits. Nutrigenetics (the science investigating the combined action of our genes and nutrition on human health) has highlighted how changes in the DNA can affect the way we process food. A well-known example is lactose intolerance, where the loss of function in the lactase enzyme hinders the digestion of dairy products. Now, a pioneering study published in the journal Clinical Gastroenterology & Hepatology, suggests that genetic variations in human carbohydrate-active enzymes (hCAZymes) may similarly affect how IBS patients respond to a carbohydrate-reduced (low-FODMAP) diet.

Research work led by Professor Mauro D’Amato from the Gastrointestinal Genetics Research Group at ClC bioGUNE in Derio, Spain and involving the Institute of Clinical Molecular Biology (IKMB) at Kiel University (CAU) and the University Medical Center Schleswig-Holstein (UKSH), Kiel Campus, has investigated the role of hCAZymes in relation to irritable bowel syndrome. In a large-scale European research network, the GenMalCarb consortium, the team has now been able to show that individuals with hypomorphic (defective) variants in hCAZyme genes are more likely to benefit from a carbohydrate-reduced diet. The study, involving 250 IBS patients, compared two treatments: a diet low in fermentable carbohydrates (FODMAPs) and the antispasmodic medication otilonium bromide. Strikingly, of the 196 patients on the diet, those carrying defective hCAZyme genes showed marked improvement compared to non-carriers, and the effect was particularly pronounced in patients with diarrhea-predominant IBS (IBS-D), who were six times more likely to respond to the diet. In contrast, this difference was not observed in patients receiving medication, underscoring the specificity of genetic predisposition in dietary treatment efficacy.

“These findings suggest that genetic variations in hCAZyme enzymes, which play a key role in digesting carbohydrates, could become critical markers for designing personalized dietary treatments for IBS” comments Dr. Britt-Sabina Löscher from the IKMB, co-author of the study. “The ability to predict which patients respond best to a carbohydrate-reduced diet has the potential to strongly impact IBS management, leading to better adherence and improved outcomes”.

In the future, incorporating knowledge of hCAZyme genotype into clinical practice could enable clinicians to identify in advance which patients are most likely to benefit from specific dietary interventions. This would not only avoid unnecessary restrictive diets for those unlikely to benefit but also open the door to personalized medicine in IBS. The research team emphasizes the need for further studies to validate these findings and delve deeper into the biological mechanisms at play. If confirmed, this approach could dramatically improve the treatment of IBS and similar gastrointestinal conditions, making dietary and therapeutic strategies more precise and effective.

The study involved researchers and clinicians from Spain (CIC bioGUNE), Italy (LUM University and University of Naples), Germany (IKMB and University of Hannover), Belgium (TARGID) and UK (University of Nottingham), and received funding from the Spanish Government MCIN/AEI/10.13039/501100011033 (PCI2021-122064-2A), the German Federal Ministry for Education and Research BMBF (01EA2208B and 01EA2208A) and the Medical Research Council MRC (MR/W031213/1), 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), the Spanish Government MCIN/AEI/10.13039/501100011033 (PID2020-113625RB-I00), the German Research Foundation DFG (NA331/13-1 and 390884018), and the Belgian Health Care Knowledge Centre (ref number: 16001).

Reference: Andreea Zamfir-Taranu, Britt-Sabina Löscher, Florencia Carbone, Abdullah Hoter, Cristina Esteban Blanco, Isotta Bozzarelli, Leire Torices, Karen Routhiaux, Karen Van den Houte, Ferdinando Bonfiglio, Gabriele Mayr, Maura Corsetti, Hassan Y Naim, Andre Franke, Jan Tack and Mauro D’Amato. Functional variation in human CAZyme genes in relation to the efficacy of a carbohydrate-restricted diet in IBS patients. Clin Hepatol Gastroenterol DOI: https://doi.org/10.1016/j.cgh.2024.09.004.

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