Gluten effects on nonceliac gluten sensitivity -what you need to know?

Gluten effects on nonceliac gluten sensitivity -what you need to know?

You will see today there is lots of talking about gluten, gluten free foods. You may also know about gluten sensitivity in celiac disease. But that is not the end. In present there are also rising concern of nonceliac gluten sensitivity. A group of people without having celiac disease also have nonceliac gluten sensitivity (NCGS). So, why those talking, what are the gluten effects on nonceliac gluten sensitivity. Is it only gluten? What are the other players? What measure you can take? Let’s find.

What is actually gluten?

Gluten refers to a complex group of proteins found in some grains including wheat. The word gluten comes from glue. When mix with water gluten tends to form a sticky cross-linked network of proteins. It acts like binder and allow bread to rise when baked. (1) Specifically gluten contains two types of protein known as gliadin and glutenin.

Human lacks enzyme for complete digestion of gluten proteins gliadins and glutenins.(2)Studies reported these proteins possess differential immune targets that make them immunotoxic in nature as they have potential to call immune action. (3) Major sources of gluten include as wheat, barley, rye, and spelt. (4) Also some oats may contain higher gluten content due to diversity.

History of gluten

Origin of grain goes about 11000 year back to the agricultural revolution when prehistoric communities started transition from hunter-gatherer to farmer. That was a relatively newer addition to human diet in comparison to 2-million-year history. (5)

Celiac disease

Celiac disease, an auto-immune disease that affects the small intestine. Ingestion of gliadin fraction of wheat gluten and similar alcohol-soluble proteins (prolamines) of barley and rye in genetically susceptible subjects causes small bowel inflammation. That further leads to subsequent immune reaction in development of celiac disease. (6) In celiac disease individuals can not absorb nutrients properly due to damage intestine.

Non Celiac gluten sensitivity (NCGS)

A larger group of individuals of around 10-15% of the population who report a wide-range of gastrointestinal symptoms that respond well to a ‘gluten-free diet’, but don’t have coeliac disease – so called ‘non-celiac gluten sensitivity (NCGS).(7) Numbers of high quality RCT study along with isolated gluten found gluten can even create problem to people who does not have celiac disease.(8,9,10, 11)

Common Symptoms of NonCeliac Gluten Sensitivity

If you have problem in gut you may have symptoms not only in gut but also nearly every other tissues of your body. Common symptoms of NCGS may include:(12,13, 14)

  • Gas, bloating and abdominal pain, discomfort
  • Diarrhea or constipation
  • Nausea
  • Lack of well being
  • Headache
  • Mental condition like Brain fog, depression, anxiety
  • Joint pain
  • Numbness in the legs, arms or fingers
  • Fatigue or tiredness
  • Dermatitis or skin rash, canker sores
  • Weight change
  • Asthma

Gluten or Wheat or FODMAPs sensitivity?


Although gluten contributes to the major portion wheat protein also have other form of protein. Clinical data also suggest existence of Non-celiac wheat sensitivity (NCWS or WS). The WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls.(15, 16)


FODMAP stands for Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols, type of commonly malabsorbed carbohydrates. Due to resistant to digestion FODMAPs reach intestine and gut bacteria then use these carbohydrates as fuel for them. FODMAPs are also fiber and prebiotics that feed bacteria. Although FODMAPs may not be sensitive to all it can act negatively in people with IBS. Specifically individual with SIBO or Small intestinal bacterial overgrowth should go for low FODMAPs diet as it fuels bacterial growth. Symptoms include gas, bloating, abdominal discomfort, diarrhea and some others.

Common FODMAPs

  • Fructans: Varying amount in many foods, common in wheat, spelt, rye and barley
  • Galactans: Mostly in legumes, beans
  • Fructose: Some fruits contains high amount of fructose. Mostly added sugar, table sugar (Know more about negative health effects of added sugar and sugar alternatives)
  • Lactose: A carbohydrate from diary source
  • Polyols: In some fruits and vegetables with varying amount, also used as sweetener

Research Findings on FODMAPs

FODMAPs also have recently been postulated as the culprit component for NCGS in wheat, instead of gluten.(17) In a RCT study of 59 individuals with self-reported non-celiac gluten sensitivity found fructans rather than gluten to induce symptoms of IBS. (18) Other study has also reported that FODMAPs, and not gluten, triggered symptoms in NCGS. (19)

Overlapping in symptoms

It is still a matter of debate whether NCGS is caused by gluten or other components of wheat. FODMAPs may also play roles in development of NCGS. Wheat also contains part of FODMAPs. Gluten represents major percentage of the total amount of gluten-containing cereals like wheat, rye, barley, and their derivatives. Apart from gluten more specifically gliadin protein other proteins named Amylase-trypsin inhibitors calls immune action. (20)

People with gastrointestinal disorder like IBS had clearly shown gluten sensitivity and removing gluten could improve their symptoms. (21) And the evidences are going stronger. A 2019 study published in the Journal of Psychiatry and Neuroscience suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with mental disorder like schizophrenia.(22)

However there are overlapping in symptoms between NCGS and other gastrointestinal disorders.(20,23)

Overall research suggests that gluten, other wheat proteins, and FODMAPs mainly fructans triggered immune reaction and a microbiota imbalance. Therefore gluten/wheat-free and low FODMAPs diet can be better strategy in such cases. (24,25)

Gluten, FODMAPs, Gut microbiota and NonCeliac Gluten sensitivity: what you need to know?

Gluten, Zonulin and Intestinal permeability

Dr. Alessio Fasano, a pediatric gastroenterologist and researcher and team from the University of Maryland School of Medicine discovered zonulin a intestinal tight junction protein .(26) Zonulin regulates intestinal barrier function which allows absorption or passing of digested nutrients, electrolytes and on the other hand prevent passage of pathogens as well as large molecules though barrier. And up regulation of zonulin open up intestinal epithelial paracellular pathway and loss barrier function. That can lead to increased intestinal permeability or leaky gut. Which further results in development of chronic inflammation, immune reactions and many autoimmune diseases. (27)

And two identified powerful triggers that can trigger zonulin release in intestine includes as small intestinal exposure to bacteria and gliadin fraction of gluten protein. (28) Gluten can damage your intestine that can lead to damage to other organs.(29) And your small intestine is not designed as home for too much bacteria more dangerously pathogenic bacteria. Therefore you need balance here.

Is there any problem with modern wheat?

There are no such concluding results. Wheat contributes to a major part of diet in many populations. Keeping aside genetic modification(which need to be avoided) lots of factors come to play e.g. breeding, change of environment, rainfall, use of pesticides.

A study published in International Journal of Food Sciences and Nutrition, mentioned that Celiac-triggering gluten proteins are indeed expressed to higher levels in modern cereals while non-triggering proteins are expressed less. (30) One study published in European Journal of Agronomy made comparison in gluten protein composition between old and modern durum wheat in relation to 20th century breeding in Italy. In their conclusion, durum wheat breeding carried out in Italy during 20th century seems to have improved wheat gluten quality in relation to both technological performance and allergenic potential. (31) In recent study on 42 patients a specific organic durum wheat variety had shown to reduce NCGS than normal commercial wheat.(32)

However, given the limited number of human trials, it is not possible to definitively conclude that ancient wheat varieties are superior to all modern counterparts in reducing chronic disease risk. (33)

On the other hand although other proteins Amylase-trypsin inhibitors (ATIs) represent up to 4% of total protein can contribute to the activation of immune cells. ATIs may have acted as interfering contaminant of gluten and appear as potential activator of innate immunity in NCGS patients. And interestingly, the amount of ATIs is increased in some modern wheat, rye, and barley compared with older wheat variants. (20,34)

Does gut microbiota have any role here?

Gut microbiota play a major rules in over all health-that has been established already in many studies. Science is yet to find many more about this ecosystem.

There is enough evidence to suggest that the gut microbiota plays a role in the onset and clinical manifestations of celiac disease and gut health maintenance.(35) In research at McMaster University had found mall intestinal bacteria exhibit distinct gluten metabolic patterns in vivo, increasing or reducing gluten induced immune reaction. P aeruginosa is known as a pathogenic bacteria that causes infection. P aeruginosa also modified gluten peptides and activated gluten-specific T-cells immune action from CD patients. In contrast, Lactobacillus from the duodenum of non celiac disease individuals degraded gluten peptides produced by human as well as P aeruginosa proteases. And thus Lactobacillus helps in reducing their immunogenicity and balances the situation. (36,37) 

A 2017 published researched in the journal of Research in Microbiology found gluten-degrading bacteria in the human small intestine.(38) Researchers even found gluten degrading enzymes in oral microbes. (39) Study also has shown multi strain probiotics containing both Lactobacillus and Bifidobacterium family helps to breakdown proteins responsible for wheat allergy.(40) In conclusion, the human intestine exhibits a large variety of bacteria capable of utilizing gluten proteins and peptides as nutrients. Thus helps us to sustain against adverse reactions of such proteins. On the other hand pathogenic like P. Aeruginosa activated gluten-specific T-cells mediated immune action. (41,42) 

And lactobacilli had shown to degrade Wheat Amylase Trypsin Inhibitors to reduce intestinal iysfunction induced by immunogenic wheat proteins. (43)

Bottom Line

In diagnosis of NCGS, the lack of standardized biomarkers remains an important challenge till date. (44)

Although gluten may not create problem to all it can create problems for a group. But if you are one with NCGS, restricting or controlling such wheat or gluten containing foods or FODMAPs can help. Also gliadin fraction of gluten protein stimulates zonulin that can lead to increase intestinal permeability and further lead to autoimmune diseases. Small amount of gluten may not harm that way but regular intake of large amount may create problem. Low FODMAPs diet specifically helps in condition like SIBO or IBS.

Wheat was also eaten in past. Comparatively NCGS reporting is new. However we have other grain also to replace these high gluten containing grain. One reason may be our previous generation had healthy gut environment with harbor of diverged gut microbiota. With direct attachment with nature, forest area they could be able to maintain a balanced healthy ecosystem. Mother nature has tremendous contribution in development of ecosystem-that is well researched. We are taking industrial pollutants in exchange of nature’s touch. We are living in sterile life. In present days use of excessive anti bacterial products are in question. Better to use plain soap and water. (45)I am not opposing industrial growth but we need balance of life. We definitely don’t aspect a planet of lifeless machines in future.

And there are rising incidence of gastrointestinal problems. (46, 47) Many diets have been evaluated to address gut health. However many diets are restrictive. After normalizing gut health you may return back to optimal diet. Probiotics helps but its extent of effects depends how and when you use it.

Many factors affect negatively to gut health

Apart from processed foods, food additives, sugar, food allergens, alcohol etc stress is directly connected to the gut health. Prebiotics FODMAPs can also act negatively if you have SIBO or bacterial overgrowth. Bacterial composition was altered with use of medications like antibiotics, NSAIDs, stomach acid neutralizer and some others.(48) These are medical tools and use should be only under medical guidance. And we can’t borrow other’s gut ecosystem. So combination of genetic and environmental factors play roles in migrant populations.(47)

Read more:

Guide to read tricky food nutrition label.

9 reasons why you should avoid sugar and sugar alternatives

Disclaimer: Information provided here are generalized information for 
educational purpose only,  not intended to provide one to one health 
consultation or replace practice of a qualified practitioner. Different 
people may have different health condition and may have different reaction 
to the same food. Hence it has been advised to consult with health care 
provider before application of any of above guidelines.
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Bikramjit Konwar

Author: Bikramjit Konwar


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