Mucosal Eosinophilia –A Marker for Nonceliac Wheat Sensitivity?

A recent prospective study (A Carrocio et al. Gastroenterol 2019; 17: 682-90) with 78 patients who were diagnosed with “nonceliac gluten or wheat sensitivity” (NCGWS) by double-blind challenge had duodenal and rectal biopsies collected and analyzed. More commonly NCGWS is referred to as NCGS.

Key findings:

  • Duodenal tissues from patients with NCGWS had hihger numbers of eosinophils than non-NCGWS controls as did rectal mucosa.  Other elevated markers included epithelial CD3+ T cells, and lamina proppria CD45+ cells.
  • Rectal mean eosinophil infiltrations was more than 2.5-fold the upper limit of normal and it was almost 2-fold increased in the duodenum.
  • Sensitivity and specificity of rectal eosionphilia, defined by >9 eos in the lamina propria) was 94% and 70% respectively.

My take: This study is intriguing but needs more confirmation. Overall, it appears that the frequency of NCGS is very low.

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Synagogue of Santa María la Blanca. Toledo Spain

The Latest on Pediatric Nonceliac Gluten Sensitivity

 A recent study (R Francavilla et al. Am J Gastroenterol advance online publication, 30 January 2018; doi: 10.1038/ajg.2017.483 ) examined “non-celiac gluten sensitivity” (NCGS) in a multicenter prospective trial from Italy (2013-16). 

This study included 1,114 children with chronic gastrointestinal symptoms and negative for both celiac disease and wheat allergy.  To determine if these children, had  a positive correlation between symptoms and gluten ingestion they were evaluated consecutively through the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge.

Design: If there was a correlation between symptoms and gluten ingestion, then patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.

Key findings:
  • Out of 1,114 children, 96.7% did not exhibit any correlation with gluten ingestion.
  • Among the 36 patients who seemed to show a correlation between gluten ingestion and symptoms, 28 patients entered the DBPC gluten challenge. Of these 28 children, eleven children (39%) tested positive.
  • “No predictive laboratory tests can help in identifying NGCS”

Also, it is worthwhile to quote the authors from their last paragraph: “philosopher Immanuel Kant [said], ‘all our knowledge begins with the senses, proceeds then to understanding, and ends with reason’. NCGS begins in the gut feeling of patients, and we are still in the process of understanding it, hoping that reason is not too far behind.'”

My take: This study shows that very few children (<4%) with chronic gastrointestinal symptoms had correlation with gluten ingestion. Even in this group, NGCS was excluded with a DBPC in >60% of cases.

Fructans, not Gluten, Inducing Symptoms In Patients with Reported Non-Celiac Gluten Sensitivity

As with yesterday’s post, today’s study (GI Skodje et al. Gastroenterol 2018; 154: 529-39) implicates fructans, not gluten, as a culprit in increasing symptoms in those with self-reported non-celiac gluten sensitivity (NCGS).

These researchers performed a double-blind crossover challenge in 59 individuals who had instituted a gluten-free diet (GFD). The symptoms were assessed with a Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) through 3 challenges –gluten, fructan, and placebo.

Key findings:

  • GSRS-IBS mean values for gluten 33.1, for fructan 38.6, and placebo 34.3.  The overall GSRS-IBS value for fructans was significantly higher than for gluten P=.04
  • GSRS-IBS mean values for bloating with gluten 9.3, for fructan 11.6, and placebo 10.1

In a related editorial (K Verbeke, pages471-3), the commentary notes that  alpha-amylase-trypsin inhibitors (ATIs) may be another factor which contributes to symptoms in those with reported NCGS.  ATIs protect plants from pests/parasites by inhibiting their digestive enzymes.  They also resist proteolytic degradation in the human intestine and are known to be potent activators of innate immune cells.

My take: This is yet another study showing that among individuals with NCGS that a GFD is often unnecessary and ineffective.  Fructans are more likely to induce gastrointestinal symptoms; however, their are likely to be several food components which contribute to GI symptoms & sometimes extra-intestinal symptoms.

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“Is There a Downside to Going Gluten-Free if You’re Healthy?” Yes

From NY Times: Is There a Downside to Going Gluten-Free if You’re Healthy?

Yes. This short commentary explains a lot of reasons why going gluten-free is not a great idea for healthy individuals.

  1. Often, a gluten-free diet incorporates more fat, more sugar, more salt and less fiber –all bad for your health.  A gluten-free diet can increase the risk of weight gain, type 2 diabetes, and cardiovascular disease.
  2. A gluten-free diet may make definitive testing for celiac disease inaccurate after more than a few weeks.
  3. “While much has been written in books and online sources about the purported benefits of avoiding gluten, such as weight loss, cognitive well-being and overall wellness, these claims are not supported by evidence….Though some patients with irritable bowel syndrome, or I.B.S., may see symptoms improve after cutting out gluten-containing foods, research suggests it’s likely to be a result of something other than gluten.”

My take (borrowed): “There’s no reason for someone who feels well to start a gluten-free diet to promote wellness,” said Dr. Benjamin Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University. “It is not an intrinsically wellness-promoting diet.”

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What Happens When Patients With ‘Gluten Sensitivity’ Are Challenged with Gluten?

A recent review of double-blind, placebo-controlled trials (n=10) (J Molina-Infante, A Carroccio. Clin Gastroenterol Hepatol 2017; 15: 339-48) showed that most individuals who consider themselves to have nonceliac gluten sensitivity (NCGS) do not show gluten-specific symptoms.  Only 16% (38 of 231) showed symptoms specific to gluten ingestion.  In addition, the authors describe a 40% nocebo response (similar or increased symptoms in response to placebo).

My take: Due to the absence of a reliable test for NCGS, there are a lot of people who avoid gluten when gluten is not the main culprit for their symptoms.

On a related topic –NPR reports on colleges developing a New Niche -Gluten-free Dining Rooms.  An excerpt:

An estimated 5 to 10 percent of college students have celiac disease or other gluten-related disorders, according to Dr. Alessio Fasano, director of the Center for Celiac Research and Treatment in Boston…

There’s also a marketing angle in responding to the rising rate of gluten-related diagnoses. “Families tell us that Kent has become a top contender because this option exists

Also from NPR –For People With Celiac Disease -Could a Viral Infection Be a Trigger?

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Zonulin –Possible Biomarker for Gluten Sensitivity?

A recent abstract indicated that there are high levels of zonulin in patients with gluten sensitivity as well as in patients with celiac disease.  These results are preliminary but could indicate a potential biomarker for this condition.  Here is a link to a review of these findings from NPR which includes commentary from Alessio Fasano: A Protein In The Gut May Explain Why Some Can’t Stomach Gluten

An excerpt:

Zonulin is an inflammatory protein first discovered by Fasano and his team in 2000. It helps regulate leakiness in the gut by opening and closing the spaces or “junctions” between cells in the lining of the digestive tract…

Giovanni Barbara and a team of researchers at the University of Bologna measured blood levels of zonulin in four groups of individuals: those with celiac disease, those with irritable bowel syndrome marked by diarrhea, those with self-diagnosed gluten sensitivity and healthy volunteers. Both celiacs and gluten sensitives turned up with remarkably high levels of zonulin in their blood. Those with IBS had elevated levels but less than half of celiacs or gluten sensitive individuals. Healthy volunteers had negligible blood levels of zonulin.

The results were presented in October as an abstract at the 23rd United European Gastroenterology Week in Barcelona, Spain.

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The Science Behind IBS Dietary Interventions

A succinct review (BE Lacy. Clin Gastroenterol Hepatol 2015; 13: 1899-1906) reviews the topic of dietary interventions for irritable bowel syndrome (IBS).

Here are some of the points:

  • “True food allergies are present in 1% to 4% of the US population, but are not more prevalent in IBS patients.”
  • One study found that “more than 1 in 4 patients with self-reported NCGS [nonceliac gluten sensitivity] actually fulfill the diagnosis.”  In other words, most patients with self-reported NCGS do not have NCGS.
  • “The prevalence of lactase deficiency is similar, or slightly higher, in IBS patients compared with healthy subjects; however, the self-reporting of symptoms attributed to lactose intolerance is not reliable.”
  • Potential mechanisms of food triggering GI symptoms were discussed, including intestinal permeability, visceral hypersensitivity, small intestine bacterial overgrowth, and gut microbiome.

Another article which covers the same topic: PR Gibson et al. Gastroenterol 2015; 148: 1158-74.