Irritable Bowel Syndrome and Gluten Sensitivity Without Celiac Disease: Notes from the Front Lines

Celiac.com 05/14/2012 - Should gluten sensitivity be thought of as “celiac light,” as just one of the milder manifestations within the wider spectrum of celiac disease? Some doctors and researchers think so.

Over the past several years, there has been increasing discussion concerning gluten sensitivity as a possible cause of irritable bowel syndrome (IBS) symptoms in patients for whom celiac disease has been excluded. 

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This is undoubtedly because gluten sensitivity, like IBS, is a symptom-based condition of diverse pathogenesis. As discussed, some have argued that gluten sensitivity might be best thought of as “celiac light,” representing the milder domains of the celiac disease spectrum.

However, there are some data to suggest that a subset of patients with gluten sensitivity may actually belong to the spectrum of celiac disease.

In a recent letter to the editors of the American Journal of Gastroenterology, doctors Courtney C. Ferch and William D. Chey of the Division of Gastroenterology at the University of Michigan Health System in Ann Arbor, Michigan, comment at length on the latest findings regarding Irritable Bowel Syndrome and gluten sensitivity without celiac disease.

Ferch and Chey note that gluten sensitivity is one of the most rapidly growing sectors in the food industry, with gluten-free products accounting for $1.31 billion in U.S. sales alone in 2011. Those sales are expected to exceed $1.6 billion by 2015.

Major food manufacturers such as General Mills and Betty Crocker, along with popular restaurant chains like PF Chang's and Subway are busy introducing new gluten-free options, or retooling original products into gluten-free versions.

People with gluten sensitivity typically show symptoms after eating gluten, but show no evidence of celiac disease or food allergy.

Unlike celiac disease, there are no accepted biomarkers for gluten-sensitivity. Doctors diagnose the condition mainly by looking at the connection between eating gluten and the presence adverse symptoms.

Numerous studies on gluten sensitivity suffer have included small sample size, a lack of adequate controls, a lack of blinding, and the use of non-validated outcome measures. Even with these limitations, Ferch and Chey say there are several studies worthy of further consideration.

One of the studies discussed in the Ferch and Chey was a double-blind, placebo-controlled, dietary re-challenge trial performed by Biesiekierski et al. The study sought to better understand the role of gluten ingestion in the development of gastrointestinal (GI) and non-GI symptoms in patients diagnosed with IBS.

The Biesiekierski study included a sample of 34 patients diagnosed with IBS by the Rome III criteria who had experienced symptom improvement with a gluten-free diet for 6 weeks before study enrollment. Celiac disease had been excluded in all study participants by either a negative HLADQ2/HLA-DQ8 haplotype or a normal duodenal biopsy. The study excluded patients with conditions such as cirrhosis, inflammatory bowel disease, non-steroidal anti-inflammatory drug ingestion, or excessive alcohol.

Over a six week double-blind randomization phase, study participants followed either a gluten-free or gluten-containing diet that was assigned at random. Nineteen of the 34 patients ate food containing 16 g of gluten per day. The other 15 patients ate gluten-free bread and mufï¬ns. Gluten used in the study was free of fermentable oligo-, di-, monosaccharides and polyols, and its protein distribution included 2.3% nongluten, 45.7% glutenin, and 52% gliadin.

The primary outcome of the study was the proportion of patients answering “no” on over half of the occasions at the end of each week to this question: “Over the past week, were your symptoms adequately controlled?”

The study team also assessed secondary outcomes including bloating, abdominal pain, satisfaction with stool consistency, nausea, and tiredness using a 100-mm visual analog scale.

Once the study period ended, the results showed that many more patients in the gluten group compared with the gluten-free group answered “no” to the primary outcome question (68% vs 40%; P .001).

Compared with the gluten-ingesting group, those who remained gluten-free also reported signiï¬cant improvements in pain (P .016), bloating (P .031), satisfaction with stool consistency (P .024), and tiredness (P .001), although they showed similar levels of wind (P .053) or nausea (P .69).

The results of celiac antibodies at baseline and after the dietary intervention were
similar.  The team also found that diet had no effect on intestinal permeability as measured by urine lactuloseto-rhamnose ratio. Additionally, they found detectable fecal lactoferrin levels in just one patient during the treatment period.

Meanwhile, high-sensitivity C-reactive protein levels remained normal before and after the dietary intervention.

There was no difference in the level of symptoms experienced by those with and without HLA-DQ2 and HLA-DQ8 alleles. The authors felt that these data support the existence of non–celiac-associated gluten sensitivity. They concluded that gluten is in fact tied to overall IBS symptoms, bloating, dissatisfaction with stool consistency, abdominal pain, and fatigue in some patients.

In their letter, Ferch and Chey also comment on several side issues.

First, they note that a recent global meta-analyses of studies showed that patients with IBS symptoms had signiï¬cantly higher rates of celiac disease than controls. As such, they point out that the American College of Gastroenterology Task Force now recommends routine celiac blood screens for patients with diarrhea-predominant IBS and IBS with a mixed bowel pattern (grade 1B recommendation).

Secondly, they note that there has been much recent discussion around the potential role of food in IBS symptoms that has focused on celiac disease. However, they point out that much has been made over the possible role of food, and possibly celiac disease, in IBS symptoms. However, they note that data from US studies show no higher risk for celiac disease among patients with IBS symptoms and no warning signs.

Although these results are certainly intriguing and hypothesis generating, they require validation in larger, randomized, controlled trials in other parts of the world.

What is clear and important for providers to understand is that gluten sensitivity is here to stay and signiï¬cantly more likely for them to encounter in day-to-day practice than celiac disease.

Read the full letter by Ferch and Chey at the website for the  Open Original Shared Link.

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