Irritable bowel, here’s how genetic defects in carbohydrate digestion affect the diet

2024-10-15 10:14:00

A pioneering study published in the journal ‘Clinical Gastroenterology & Hepatology’ suggests that genetic variations in the human enzymes responsible for the digestion of carbohydrates (hCAZymes) may influence the effectiveness of a low-carbohydrate diet in patients with irritable bowel syndrome (Ibs). The research could lead to personalized treatments for IBS, using genetic markers to predict which patients will benefit from specific dietary interventions.

Irritable bowel syndrome – explains a note – is a digestive disorder that affects up to 10% of the world’s populationcharacterized by abdominal pain, bloating, diarrhea or constipation. Despite its prevalence, treatment of IBS remains challenging as symptoms and responses to dietary or pharmacological interventions vary significantly. Patients often link their symptoms to the consumption of certain foods, particularly carbohydrates, and reducing or eliminating them from the diet has emerged as an effective treatment option, although not all patients experience the same benefits.

The research, coordinated by Mauro D’Amato of the Department of Medicine and Surgery of the Lum ‘Giuseppe Degennaro’ University and the Gastrointestinal Genetics group of the Cic bioGune institute, investigated the role of hCAZymes genes in relation to Ibs. Through a large international collaboration (the GenMalCarb consortium) and data from the Domino study, the team highlighted that individuals with hypomorphic (defective) variants in the hCAZyme genes are more likely to benefit from a low-carbohydrate diet. In detail, the study involved 250 patients with IBS comparing two treatments: a low-carbohydrate diet (low-Fodmap) and the antispasmodic drug otilonium bromide. Surprisingly, of the 196 patients who followed the diet, those carrying defective hCAZyme genes showed a marked improvement, compared to non-carriers, and the effect was particularly pronounced in diarrhea-predominant Ibs patients (Ibs-D), who had 6 times more likely to respond to the diet. In contrast, this difference was not observed in patients treated with the drug, underlining the specificity of genetic predisposition in the effectiveness of dietary treatment.

“These results – comments D’Amato, senior author of the study – suggest that genetic variations in hCAZyme enzymes, which play a key role in carbohydrate digestion, they could become key indicators for designing a personalized diet in the treatment of IBS“.

This “is a heterogeneous and multifactorial condition, with environment, diet, microbiota, genetics and factors related to the immune system all playing an important role. It is difficult to diagnose and treat because different mechanisms predispose to the onset of symptoms that essentially indistinguishable from a clinical point of view. We have been studying the predisposition to Ibs for years – continues the professor – hoping to identify genetic factors that can allow a stratification of patients into different types and ‘molecular’ groups for better therapeutic precision hereditary forms of carbohydrate intolerance, such as lactase or sucrase deficiencies, we are finding that certain genetic defects in hCAZymes may predispose to Ibs through maldigestion of carbohydrates. This can be addressed therapeutically through their reduction or elimination from diet, focusing attention on genetically predisposed individuals”.

In the future, integrating hCAZyme genotype knowledge into clinical practice may allow 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 from them, but would also open the door to personalized medicine in IBS. The research team highlighted the need for further studies to validate these findings and delve deeper into the biological mechanisms at play. If confirmed, this approach could significantly improve the treatment of IBS and similar gastrointestinal diseases, making dietary and therapeutic strategies more precise and effective.

The study involved researchers and clinicians from Italy (Lum University and University of Naples), Spain (Cic bioGune), Germany (Ikmb and University of Veterinary Medicine of Hannover), Belgium (Targid) and the United Kingdom (University of Nottingham), and has received funding from the Spanish Government, the German Federal Ministry for Education and Research and the Medical Research Council UK, under the aegis of the European joint programming program ‘A Healthy Diet for a Healthy Life’ (Jpi HDHL) and of the Era-Net Era-Hdhl, and the Belgian Health Care Knowledge Centre.