Treatment for irritable bowel syndrome, IBS, often includes restricting certain foods, such as carbohydrates, but that doesn’t work for everyone. A new study has found that there might be a genetic reason for this, opening the door to personalized, genetically tailored diets to treat IBS.
In irritable bowel syndrome (IBS), the digestive tract looks normal but doesn’t function as it should, causing symptoms like cramping and abdominal pain, bloating, and diarrhea or constipation, or both. It’s a condition that affects up to 10% of people worldwide.
Often, dietary triggers are connected to an exacerbation of symptoms. Restricting certain carbohydrates, especially fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are poorly absorbed by the small intestine, is seen as an effective treatment option. However, it doesn’t work for all IBS sufferers. In a new international study, researchers looked at whether there was a genetic reason why lowering FODMAPs had a therapeutic effect in some but not others.
The study was led by Mauro D’Amato, a research professor from the gastrointestinal genetics research group at CIC bioGUNE, Spain, and the Department of Medicine and Surgery at Libera Università Mediterranea (LUM) University, Italy. D’Amato collaborated with scientists from the Genetic Carbohydrate Maldigestion (GenMalCarb) consortium, which is led by Dr Maura Corsetti from the University of Nottingham’s School of Medicine and also includes experts from Germany and Belgium.
The diversity of the human genome leads to the many functional differences seen between people. Genetic variations – both rare and common – can occur that are relevant to our ability to digest the sugars and starches that form a major part of our diets. The diet-related symptoms of IBS may involve the maldigestion of carbohydrates due to the inefficiency of enzymes that break down polysaccharides, which are long chains of carbohydrate molecules.
It's been found that in people with lactose intolerance, variations in the lactase gene change the protein building blocks (amino acids) of the lactase enzyme produced. This means that the body can’t fully digest the sugar – lactose – in dairy products. The researchers suspected that a similar thing was occurring in people with IBS. In humans, a diverse set of carbohydrate-active enzymes (hCAZymes) are involved in the breakdown of carbohydrates. So, the researchers investigated whether genetic variations that caused defects in hCAZymes affected how individuals with IBS responded to a low-FODMAP diet.
They undertook a retrospective genetic analysis of 250 IBS patients from the DOMINO trial who were randomized to receive either a dietary treatment (a low-FODMAP diet) or an antispasmodic medication used to relieve gut spasms caused by IBS, for eight weeks. Participants were categorized as ‘carriers’ or ‘non-carriers’. Carriers had at least one hypomorphic variant in one or more of the hCAZymes – a hypomorphic variant results in a reduced level of gene activity or a reduction in enzymes produced – whereas non-carriers had no variants.
Of the patients put on a low-FODMAP diet, those carrying defective hCAZyme genes showed a marked improvement in symptoms compared to non-carriers. The effect was particularly strong in patients with the diarrhea-predominant subtype of IBS (IBS-D), who were six times more likely to respond to the diet. This difference was absent from participants who were given the antispasmodic drug.
“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,” said D’Amato. “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.”
Using genetics to identify in advance which patients are most likely to benefit from specific dietary interventions would avoid unnecessarily restrictive dies for those unlikely to benefit and also pave the way for personalized medicine in IBS treatment.
“These data needs [sic] to be further validated by future studies,” co-author Corsetti said. “If confirmed, this approach open [sic] the way to personalized dietary and treatment strategies.”
The study was published in the journal Clinical Gastroenterology and Hepatology.
Source: University of Nottingham
