Non Coeliac Gluten Sensitivity: Intestinal Cell Damage & Systemic Immune Activation



A new research paper titled ‘Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease’, has just been published in the BMJ Open Gastroenterology Journal ‘Gut’.

Many individuals with ME/CFS have gluten or wheat sensitivity, often anecdotally reporting a decrease in some symptoms with removing gluten from their diets. Many patients also report that removing dairy or following a FODMAPs diet or other diets – have decreased some ME/CFS symptoms. However, this is not the case for everyone with ME/CFS and it is far from touted as a ‘Cure’.

This new research by Dr Armin Alaedini et all from the Department of Medicine at the Columbia University Medical Center, has some interesting findings in people who are sensitive to wheat but do not have Coeliac Disease. Note this is a different part of Columbia University from Drs. Lipkin and Hornig at the Center for Infection and Immunity.


Objective Wheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms in response to wheat ingestion, without the characteristic serological or histological evidence of coeliac disease. The aetiology and mechanism of these symptoms are unknown, and no biomarkers have been identified. We aimed to determine if sensitivity to wheat in the absence of coeliac disease is associated with systemic immune activation that may be linked to an enteropathy.

Design Study participants included individuals who reported symptoms in response to wheat intake and in whom coeliac disease and wheat allergy were ruled out, patients with coeliac disease and healthy controls. Sera were analysed for markers of intestinal cell damage and systemic immune response to microbial components.

Results Individuals with wheat sensitivity had significantly increased serum levels of soluble CD14 and lipopolysaccharide (LPS)-binding protein, as well as antibody reactivity to bacterial LPS and flagellin. Circulating levels of fatty acid-binding protein 2 (FABP2), a marker of intestinal epithelial cell damage, were significantly elevated in the affected individuals and correlated with the immune responses to microbial products. There was a significant change towards normalisation of the levels of FABP2 and immune activation markers in a subgroup of individuals with wheat sensitivity who observed a diet excluding wheat and related cereals.

Conclusions These findings reveal a state of systemic immune activation in conjunction with a compromised intestinal epithelium affecting a subset of individuals who experience sensitivity to wheat in the absence of coeliac disease.

Science Daily has covered this so far, and it would be surprising if this does not make more headlines considering the amount of people who now go gluten free in the world.

This new paper is interesting with respect to ME/CFS due to many being sensitive to gluten and other foods, and the theories regarding ‘Leaky gut’, but there are also more points of interest. There was a recent paper published about ME/CFS that analyzed similar inflammatory and immune system markers, that also highlighted microbial translocation by Dr Maureen Hanson et all from Cornell University. We posted about this recent paper titled  ‘Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome’. There seems to be some similar findings in both papers, the results section of the Hanson et all paper states:


We observed elevated levels of some blood markers for microbial translocation in ME/CFS patients; levels of LPS, LBP, and sCD14 were elevated in ME/CFS subjects. Levels of LBP correlated with LPS and sCD14 and LPS levels correlated with sCD14. Through deep sequencing of bacterial rRNA markers, we identified differences between the gut microbiomes of healthy individuals and patients with ME/CFS. We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum. In the patient cohort, we find less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory. Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as ME/CFS with a cross-validation accuracy of 82.93 %.

Some good news regarding this research by Dr Armin Alaedini, is that he has teamed up with ME/CFS specialist Drs. Bateman and Vernon from the Bateman Horne Center to work further in this area specifically on ME/CFS. A $200,000 grant from the NIH was awarded for the research, check this out on the project on the NIH reporter.