Patients Who Avoid Wheat and Gluten: Is That Health or Lifestyle?

Abstract

In a New York restaurant, a celiac patient requesting a gluten-free menu was asked by the server if the diet was for health or for lifestyle. This increasingly common exchange exemplifies the clinical conundrum clinicians face regarding the use of a gluten-free diet (GFD). Although humankind has likely existed in some form for 2.5 million years, it is only in the last 10,000 years that humans have been exposed to wheat, which was originally cultivated in the Fertile Crescent from *9000 BC to 4000 BC. Thus, wheat and therefore, gluten is a relatively novel component of the human diet. The globalization of wheat production, and subsequently its increased worldwide consumption, has increased the incidence and clinical recognition of gluten-related disorders [1]. The most notable gluten-related disorder is celiac disease (CD), a state of heightened immune response to ingested gluten in genetically susceptible individuals. Initial reports in the 1950s suggested this to be a rare condition affecting 1 in 8,000. Nevertheless, more recently, its prevalence in the United States and elsewhere is 0.71 % or 1 in 141 [2]. The sole effective treatment for CD is lifelong adherence to a strict GFD. More recently, a few case reports and series published in the 1980s described individuals intolerant to gluten, by way of experiencing irritable bowel syndrome (IBS) type symptoms, but in whom CD serologies and small intestinal biopsies were normal. Since the diagnosis or explanation for these symptoms was lacking and possibly dismissed, such patients were unclassifiable and untreatable [3]. Nonetheless, over the last few years, mounting media reports have speculated that the use of a GFD is rapidly growing to the point that it is now a big business, seemingly greatly exceeding the demand predicted from CD subjects alone. This media pressure finally prodded the scientific community into a response, led by an Australian group, who performed a landmark double-blind, randomised, placebo-controlled study reporting that gluten from two slices of bread and one muffin indeed induced gastrointestinal symptoms in subjects without CD [4]. Subsequently, a consensus of experts has introduced the term ‘‘non-celiac gluten sensitivity’’ (NCGS) to describe such subjects [5]. A subsequent flurry of research papers raised the ratio of publications for NCGS:CD from 1:438 to 1:10, to the point that NCGS is considered the new frontier of gluten-related disorders [6]. The pathophysiology of NCGS has not yet been fully elucidated. Whereas the innate and adaptive immune response to gluten is responsible for the manifestations seen in CD, only the innate immune system is seemingly triggered in NCGS. There have been promising reports of altered small bowel intestinal permeability, proliferation of peripheral blood monocytes, the presence of antigliadin antibodies, enhanced cytokine induction, and induction of basophil activation in NCGS, although these findings have not yet been confirmed [6]. Gluten is only one of the complex milieu of nutrients present in wheat, which also contains fructans, which are fermentable, poorly absorbed, short chain carbohydrates, also termed FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). FODMAPS provoke gastrointestinal symptoms in IBS patients through mechanisms involving gut microbiota, gas production, and fermentation [7]. There is also emerging evidence that wheat-amylase trypsin inhibitors are also associated with intestinal symptoms [8]. Since it is unclear which component of wheat-based products is I. Aziz (&) D. S. Sanders Department of Gastroenterology, Room P39, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK e-mail: imran.aziz@sth.nhs.uk