History has a habit of repeating itself. Just like coeliac disease and fibromyalgia before it, gluten sensitivity has attracted scepticism from certain health professionals, who are firmly convinced it amounts to nothing more than collective hysteria. For them, the reason that thousands of people have chosen to ‘go gluten-free’ is because it’s the latest food fad, and nothing else. And if these people’s ‘imaginary’ symptoms appear to be relieved by reducing their consumption of gluten, it must be the result of a placebo effect.
Are you familiar with the rhetoric? Have you been on the receiving end of it? Well be assured that it’s not going to go on for much longer. Scientists have put forward a plausible theory to explain this disorder and at the very least, it shows that sensitivity to gluten is certainly not imaginary1
. Stay with us on this one – the mechanisms are somewhat complex.
Could gluten-sensitivity soon be recognised by the scientific community?
As in the case of coeliac disease, those said to be ‘gluten-sensitive’ complain of symptoms after eating food that contains gluten. These are a combination of the symptoms of irritable bowel syndrome
, including abdominal pain, bloating, intestinal disorders (diarrhoea or constipation) and more general problems such as headaches, fatigue or muscle pain.
But unlike coeliac disease, those with gluten sensitivity do not suffer damage to their intestinal wall or produce antibodies against gluten molecules. Does this mean, then, that the disorder doesn’t exist? It’s a debate that continues to rage among the scientific community. And while some researchers prefer to focus on confirming that any apparent benefits from a gluten-free are due to a placebo effect, others are trying to identify the potential mechanisms that could explain such benefits.
A team of researchers has just come up with an explanation for the disorder
which is causing something of a buzz1
. According to them, non-coeliac gluten sensitivity (NCGS), which affects more than 15% of the population, may be the result of two combined mechanisms.
1) An imbalance in gut microbiota
Some years ago, it was discovered that our intestinal microbiota - the community of microorganisms that live in our digestive tract - plays a surprisingly significant role in our overall health, much more so than was previously thought.
For example, scientists realised that bacteria in the gut produced short-chain fatty acids (SCFAs), in particular butyrate, a nutrient that affects the growth and renewal of cells in the colonic mucosa. Without this important nutrient, colon cells die off and stop producing sufficient mucus, the protective layer that forms a physical barrier between microorganisms and harmful substances2
This is probably what happens with people who are sensitive to gluten. It seems that butyrate-producing bacteria (which normally belong to the Firmicutes phylum)3
) struggle to maintain adequate levels of butyrate – either because there are too few of them, or because of a fault in their ‘allies’, bacteria of the Bifidobacteria genus. These supply them with acetate and lactate which are then converted into butyrate 4
. If there are too few bifidobacteria, there will also be too few butyrate-producers – it’s a delicate balance.
The resulting lack of butyrate and mucus encourages contact between intestinal cells and microbial antigens. Most importantly, it disrupts one of the fundamental mechanisms of the gut mucosal barrier: bacterial translocation5-6
. This is the passage of bacteria from the gastrointestinal tract through the gut mucosa to other sites, such as the mesenteric lymph nodes, bloodstream and extraintestinal organs.
Normally, bacterial translocation is prevented via a number of mechanisms, including intestinal alkaline phosphatase (IAP), an enzyme which stops pathogenic bacteria from adhering to intestinal cells7
. But butyrate is an inducer of IAP expression8: any decrease in butyrate equally involves a fall in IAP and compromises gut mucosal permeability.
2) A diet rich in gluten and ATIs
For some time now, scientists have suspected that proteins other than gluten called amylase-trypsin inhibitors (ATIs) - present in the same foods as gluten - may also be involved in NCGS9-11
These are protein components which protect plants from parasites and pests by inhibiting digestive enzymes. As a result, they also prevent protein from being broken down in humans. In other words, just like gliadin and glutenin (which make up gluten), these compounds are very poorly digested, remaining almost intact in the lumen of the intestine.
And the real problem is that these compounds have become more and more prominent in our diet: by selecting grain varieties that are increasingly-resistant to pests, we have inadvertently increased our dietary intake of ATIs12
. When we eat gluten-rich food such as bread or pasta, we’re also consuming ATIs.
Under normal conditions, an influx of these substances, to which humans are relatively unaccustomed, presents no risk to intestinal cells, protected as they are by mucus and complex detoxifying mechanisms. But when there’s an imbalance in the gut microbiota, these defences fall apart, enabling ATIs to advance on the mucosa with impunity13
. Once there, it’s strongly suspected they bind to receptors14-15
called TLR4, located on enterocyte membranes, which normally block toxins, or molecules from pathogenic bacteria. It is this binding of ATIs to TLR4 which potentially causes gut inflammation, releasing IL-1β and TNFα cytokines, as well as causing an increase in gut permeability16
What’s more, once these substances have travelled beyond the gut mucosa, they tend to bind to the same receptors on other cells17
, increasing the inflammatory response already triggered elsewhere in the body. This could account for the extra-intestinal symptoms suffered by gluten-sensitive individuals (such as fatigue, pain and mood problems) and the speed with which they occur following consumption of food rich in gluten and ATIs.
In the absence of any intervention, a vicious circle is initiated since chronic inflammation reduces the efficacy of intestinal alkaline phosphatase (IAP), which in turn promotes the growth of pathogenic bacteria in the gut.
The good news is that if this research team’s theory is proved correct, NCGS (which should perhaps be referred to as ‘dysbiosis-induced sensitivity to gluten and ATIs’) can be cured. Unlike coeliac disease, it has no genetic cause.
To do so, it’s therefore important torestore the balance of gut microbiota
. Drawing on the conclusions of the scientists responsible for this theory, these are the steps necessary for resolving ‘gluten sensitivity’:
- Restore adequate levels of butyrate, either directly, or indirectly by supplementing with bifidobacteria-rich concentrates which encourage its production.
- Increase consumption of dietary fibre which is essential for the growth of butyrate-producing bacteria (or takenatural high-fibre supplements).
- Avoid foods high in gluten and ATIs, while restoring the balance of your gut flora, or improve digestion of them by supplementing with enzymes that can break down wheat proteins (such as those found in Glutalytic®).
- Avoid ‘gluten-free’ processed foods which, according to a study in the Journal of Human Nutrition and Dietetics, are higher in fat, sugar and salt, and lower in fibre than their traditional counterparts!
- Steer clear of foods high in saturated and trans fats and animal protein which increase bile salts, promote the growth of pathogenic bacteria and exacerbate intestinal translocation18-19.
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5. Yan, H.; Ajuwon, K.M. Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS ONE 2017, 12, e0179586.
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7. Wang, W.; Chen, S.W.; Zhu, J.; Zuo, S.; Ma, Y.Y.; Chen, Z.Y.; Zhang, J.L.; Chen, G.W.; Liu, Y.C.; Wang, P.Y. Intestinal alkaline phosphatase inhibits the translocation of bacteria of gut-origin in mice with peritonitis: Mechanism of action. PLoS ONE 2015, 10, e0124835.
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11. Cuccioloni, M.; Mozzicafreddo, M.; Ali, I.; Bonfili, L.; Cecarini, V.; Eleuteri, A.M.; Angeletti, M. Interaction between wheat alpha-amylase/trypsin bi-functional inhibitor and mammalian digestive enzymes: Kinetic, equilibrium and structural characterization of binding. Food Chem. 2016, 213, 571–578.
12. Zevallos, V.F., Raker, V., Tenzer, S. et al. Nutritional wheat amylase-trypsin inhibitors promote intestinal inflammation via activation of myeloid cells. Gastroenterology. 2017; 152: 1100–1113.e12
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17. Uhde, M.; Ajamian, M.; Caio, G.; De Giorgio, R.; Indart, A.; Green, P.H.; Verna, E.C.; Volta, U.; Alaedini, A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coelic disease. Gut 2016, 65, 1930–1937.
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