Overlap Between Non-Celiac Gluten Sensitivity and Irritable Bowel Syndrome

Despite only around 1% of the population having celiac disease, gluten-free diets and gluten-free food have exploded in popularity in the past several years. One reason for this may be other conditions that are caused or irritated by gluten or wheat. Two of these conditions are non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS). Both of these diseases lack a reliable biomarker to test or an established cause, making them difficult to diagnose. A doctor that suspects a patient has NCGS or IBS must first rule out other possibilities, such as celiac disease, and then use diagnostic criteria, the Salerno Experts’ criteria for NCGS or the Rome III criteria for IBS, to make the final decision. With the lack of a reliable diagnostic test, and the fact that wheat or gluten can trigger symptoms for both conditions, there may be significant overlap between the two.A literature review was published in the Current Opinion in Gastroenterology to further explore this possible overlap. The authors, Anupam Rej and David Sanders, saw that both NCGS and IBS have a similar prevalence of around 10%, although for NCGS, this prevalence can vary greatly depending on the study. Both conditions also predominantly affect females and young/middle-aged adults. They found a clear association between NCGS and IBS based on a large UK questionnaire with around 1000 respondents. In the study, 20% of people with self-diagnosed NCGS fit the Rome III criteria for IBS, compared to only 3.89% of people without NCGS. This difference was found to be statistically significant and could mean that people with self-diagnosed NCGS are more likely to have IBS, or that people with self-diagnosed NCGS actually have IBS instead.

Rej and Sanders also looked beyond gluten at studies involving other proteins and carbohydrates present in the wheat molecule. These compounds include amylase and trypsin inhibitors (ATIs), wheat germ agglutinins (WGAs) and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). WTIs have been found to cause inflammation in the intestines and have long been associated with baker’s asthma, a kind of occupational asthma caused by breathing in various kinds of cereals as a baker. WGAs were found to cause inflammatory responses in immune cells as well as affect intestinal cell permeability. However, these effects have not yet been properly studied in humans. FODMAPs have actually been found to help gut health, however, fructans, part of the FODMAP family cause intestinal gas and distention. This happens even in healthy patients but patients with NCGS or IBS may have colonic hypersensitivity to distention which then causes symptoms when the patient ingests fructans. Because of all these possible effects from wheat compounds besides gluten, NCGS is now sometimes referred to as non-celiac wheat sensitivity (NCWS) or nonceliac wheat protein sensitivity (NCWPS).

NCGS has been studied since the 1970s, but only recently has it been able to be formally diagnosed with the Salerno Experts’ criteria. The authors note that this diagnostic criteria still has many issues that make diagnosis difficult. The main issue is that it requires a double-blind placebo-controlled (DBPC) gluten challenge lasting at least 6 weeks to establish a baseline for that patient, followed by a gluten-free diet to compare to the baseline. Many patients will not agree to six weeks of a gluten challenge diet due to the symptoms it may cause.

There have also been recent developments in linking IBS to gluten. The authors found multiple studies where patients with irritable bowel syndrome-diarrhea (IBS-D) had statistically significant improvements on a gluten-free diet compared to a gluten challenge diet. Studies like these are more evidence of the overlap between IBS and NCGS and that patients with IBS may benefit from a gluten-free diet. However, many studies on how wheat and gluten affect IBS and NCGS were heterogeneous, meaning they used differing amounts of gluten, differing durations, and differing amounts of other variables that make it more difficult to compare the studies. The authors suggest that future studies need to be more robust and also more homogeneous so that the actual wheat component that causes IBS and NCGS symptoms can be found, as well as the exact differences between these two similar conditions.

The authors conclude that the literature supports the idea that there is significant overlap between NCGS and IBS. They also found that gluten may not be the only culprit and that other wheat compounds such as ATIs or WGAs also play roles that might be the key to the difference in how NCGS and IBS are affected by eating wheat. Further studies that use better and more homogeneous designs are key to finding out these roles as well as eventually identifying good biomarkers so that these conditions can be more easily diagnosed.