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.