This short article provides an overview of the differences in microbiota which exist in gluten-related disorders, with a particular focus on coeliac disease. It goes on to outline a planned controlled prospective study which examines changes in intestinal microflora in patients with wheat sensitivity.
The increasing prevalence of food intolerances, especially in relation to certain carbohydrates, represents a global health problem. [1] Moreover, intolerance of gluten and gluten-bound substances, e.g. amylase-trypsin inhibitor (ATI) is blamed [2] for intestinal (e.g. meteorism, pain, constipation, diarrhoea) and extraintestinal symptoms (e.g. fatigue, headaches, joint pain, skin irritation) in affected patients. [3] The pathogenesis of food intolerances is blamed on factors such as changes in the composition of the intestinal flora and its influence on mucous membrane immune tolerance. [4]
The intestinal barrier is important to maintain homoeostasis in the intestine. If intestinal imbalance occurs, the intestinal barrier can be attacked and become permeable as part of leaky gut syndrome. It has been shown that there is an association between leaky gut syndrome and the development of gastrointestinal disease and possibly food intolerances. [5]
The microbiome of the human digestive tract therefore also appears to play an important role in influencing wheat/gluten-associated disease. [4]
It is common knowledge that the intestinal microflora is dependent on many factors. The microbial composition in the small intestine is primarily determined by the competition between micro-organisms and the host to ensure rapid absorption and utilisation of carbohydrates. The micro-organisms in the colon, on the other hand, are affected by both the complex utilisation of carbohydrates and competition among themselves. [6]
Nutrition plays an important role in this case. Mouse studies have already demonstrated that diet can rapidly alter the intestinal microbial composition. [7]
Numerous publications demonstrate the presence of streptococcus sp., E.coli, clostridium sp., GC-rich organisms, bacteroides uniformis, blautia glucerasea and bifidobacteria in the small and large intestine, which prefer different substrates. [8] It is interesting in this context that B. uniformis primarily utilises inulin, whereas other species primarily metabolise fructo-oligosaccharides or monosaccharides. [9]
An indication of the importance of microbial composition in coeliac disease is provided by the fact that there is a different bacterial population in these patients compared to healthy individuals. A significantly higher proportion of bifidobacterium bifidum and increased numbers of lactobacillus sp. were found in coeliac patients, but their diversity decreased significantly after maintaining a gluten-free diet. [10]
Furthermore, it was demonstrated in-vitro that certain bifidobacterium strains reduced the inflammatory immune response triggered by gliadin peptides, thus exerting a protective effect. [11,12]
In 2013, Wacklin et al. reported a possible link between the manifestation of coeliac disease in the form of gastrointestinal or extraintestinal symptoms and the microbiome. [13]
In another study, the duodenal microbiome of coeliac disease patients with persistent symptoms despite long-term GFD and normalized small-intestinal mucosa was studied in comparison with coeliac disease patients without symptoms. It was determined that there were differences in bacterial colonisation of the small intestine between patients without symptoms and patients with persistent symptoms. They had a significantly increased amount of proteobacteria, whereas the number of bacteroidetes and firmicutes was reduced. Overall, the coeliac disease patients with persistent symptoms exhibited reduced microbial diversity. In some subgroups of coeliac disease there is thus evidence of a dysbiosis as a possible cause of recurrent symptoms, in which case new treatment approaches, e.g. in the form of pro- or prebiotics, would be possible. [14]
In addition, Smecuol et al. have already investigated the effect of the probiotic bifidobacterium infantis Natren Life Start Strain Super Strain on the clinical progress of untreated coeliac patients. Of the 22 patients, 12 were given 2 B. infantes capsules and 10 were given 2 placebo capsules with meals. While taking the probiotic had no effect on intestinal permeability, symptoms of dyspepsia, constipation and gastro-oesophageal reflux improved significantly in the B. infantis group. There was also a significant increase in MIP-1ß (macrophage inflammatory protein-1ß) in the probiotics group. Although this study thus indicates a possible mitigating effect of probiotics on some coeliac disease symptoms, it requires confirmation by further studies. [15]
A recent study by Olivares et al. in patients with a high genetic risk of coeliac disease revealed an altered microbial composition even in infancy and early childhood, which is an indication that the change in the microbiome might take place at a very early stage. Compared to infants without increased coeliac risk, a significantly higher number of firmicutes and proteobacteria, and a smaller number of actinobacteria, were found in HLA-DQ2-positive carriers. The number of bifidobacteria species was also reduced. A genetic predisposition in the form of HLA-DQ2 thus appears to have an impact on the microbiome and could as such also contribute to the pathogenesis. This finding could be useful in determining the risk of coeliac disease. [16]
Generally, this data indicates that a link exists between the pathogenesis and the symptoms of gluten-related diseases and the human microbiome. However, the extent to which certain bacterial species are involved in the pathogenesis of coeliac disease or non-coeliac gluten sensitivity (NCGS), and the extent to which damaged mucosa provide preferential living conditions for these bacterial species, is still unclear and requires further investigation.
The initial data from Biesiekierski et al. (2013) allows us to speculate that fermentable carbohydrates are also the cause or at least an influencing factor in patients with wheat sensitivity. Therefore, we consider that it would be of particular interest to determine the differences in microbial colonisation between patients and healthy controls. In the context of a controlled prospective study, we are therefore examining changes in intestinal microflora in patients with documented wheat sensitivity with a mixed diet, gluten-free diet and low-FODMAP diet to determine the influence of carbohydrate chains on bacterial growth and differentiation thereof. The comparison with a healthy control group and a control population with proven coeliac disease is used for better differentiation between the bacterial strains that are responsible for the pathogenesis of wheat sensitivity.
The detection of the specific composition of flora in patients with wheat sensitivity could represent an innovative approach for targeted probiotic treatment with few side effects.
Authors
PROF. DR. MED. YURDAGÜL ZOPF
Medical Clinic 1, University of Erlangen, Germany
PRIV. DOZ. DR. RER. NAT. WALBURGA DIETERICH
Scientific employee Medical Clinic 1 University Erlangen, Germany
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