Recently this I09 article about wheat made the rounds and there was a part in it that stood out to me:

According to Alessio Fasano, the Medical Director for The University of Maryland's Center for Celiac Research, no one can properly digest gluten.

"We do not have the enzymes to break it down," he said in a recent interview with TenderFoodie. "It all depends upon how well our intestinal walls close after we ingest it and how our immune system reacts to it." His concern is that the gluten protein, which is abundant in the endosperm of barley, rye, and wheat kernels, is setting off an aberrant immune response.

I am not an expert in the matter, but my understanding is that the very etiology of celiac involves the breakdown of gluten (specifically the gliadin) by tissue transglutaminase, which is definitely an enzyme*.

However, in some instances, TG2 can react with water in preference over an amine, leading to the deamidation of glutamine residues. 118,119 Gluten proteins, the immunological trigger of gluten sensitivity, are glutamine-rich donor substrates amenable to deamidation. TG2 contributes to disease development in at least two ways: fi rst, by deamidating gluten peptides and thereby increasing their affi nity for HLA-DQ2/DQ8, which potentiates the T-cell response, 120,121 and, second, by haptenisation of self-antigens through crosslinking with gliadins. 122 This latter activity has been implicated in autoantibody development (fi gure 4). Activation of TG2 and deamidation of gluten peptides seems to be central to disease development and is now well understood at a molecular level.

In fact, it's my understanding that testing for celiac often involves looking for those Anti-transglutaminase antibodies. So it's an enzyme that normally breaks down gluten and the process has gone haywire. If we have an enzyme able to do this, wouldn't that allow normal people to break down gluten? Am I misunderstanding things?

I do find info that gluten tends to be hard for the human digestive system to break down**

Because human gastric and pancreatic enzymes lack postproline cleaving activity, the abundance of proline residues in gluten renders it highly resistant to complete proteolytic degradation in the human gastrointestinal tract, a feature that is most likely linked to the disease-inducing properties of gluten.

But no evidence that this has negative effects on healthy people since most plant foods contain things we can't break down

*Gluten sensitivity: from gut to brain. Marios Hadjivassiliou, David S. Sanders, Richard A. Grünewald, Nicola Woodroofe, Sabrina Boscolo, Daniel Aeschlimann Lancet Neurol. 2010 March; 9(3): 318–330. doi: 10.1016/S1474-4422(09)70290-X

** Combination Enzyme Therapy for Gastric Digestion of Dietary Gluten in Patients With Celiac Sprue Jonathan Gass, Michael T. Bethune, Matthew Siegel, Andrew Spencer, Chaitan Khosla Gastroenterology 1 August 2007 (volume 133 issue 2 Pages 472-480 DOI: 10.1053/j.gastro.2007.05.028)

  • So further research shows deamidase and transaminase act on parts of gluten, but there are other parts ( polyproline/glutamine) that are resistant to these type of enzymes.
    – Melissa
    Dec 20, 2012 at 18:23
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    This has garnered an impressive number of upvotes for an otherwise disregarded (= no answers, no comments) post. I just wonder: wouldn’t this be better suited on biology.stackexchange.com? Then chance of getting a qualified answer would probably be better there. Dec 21, 2012 at 1:46
  • I heard from my dr. that wheat has been genetically modified to contain more protein. That may be the reason we r seeing an upsurge in gluten sensitivity.
    – user15855
    Oct 17, 2013 at 8:27
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    @Miriam: you may want to look at this answer at about.com. I thought of making a question on this topic, but it seemed pointless if I'd include this link in the question. Another item if interest is that people have been eating purified and processed wheat gluten for ages, so exposure to high concentrations of gluten is nothing new, though it may be more common now.
    – adam.r
    Nov 23, 2013 at 11:46

3 Answers 3


Yes, healthy people are capable of digesting wheat gluten.

In this study they were attempting to compare the digestibility of several proteins in humans and rats. We are only interested here in gluten and humans.

Here's an extract from Table 4.

Extract from Table 4

It shows that, depending on which measurement system they used, wheat gluten protein was 80-100% digestible by (healthy) humans.

A paper from back in 1949 calculated gluten digestibility using a fairly new (at the time) technique: Nitrogen Balance Indices, to see whether consuming Lysine would help.

The mean nitrogen balance index for gluten was 0.62. For gluten plus lysine, it was significantly higher, 0.76, approach ing the value for casein. Thus lysine, was shown to enhance the nutritive value of gluten for humans, as it had previously been shown to do for lower animals.

  • @Melissa: Have I answered the question here to your satisfaction? I've largely ignored the papers you have cited casting doubt over the mechanisms to look at the results of digestion - the nitrogren in the gluten being taken up by the body.
    – Oddthinking
    Dec 26, 2012 at 0:30
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    The only thing I would add is some comment about human heterogeneity on gluten digestion. Clearly some people are so intolerant of it they can't eat it (this is the definition of coeliac disease).
    – matt_black
    Oct 17, 2013 at 10:55
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    Celiac is not a matter of able to digest or not. Celiacs are able to get energy from gluten, it just causes a serious autoimmune reaction. If they really couldn't digest it, they would be better off since they would not have reactions to an enzyme that breaks gluten down, transglutaminase.
    – Melissa
    Dec 3, 2013 at 16:17
  • @Melissa: An interesting point, but I am not sure that it is relevant to this question.
    – Oddthinking
    Dec 3, 2013 at 22:39
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    I was responding to matt black's contention
    – Melissa
    Dec 4, 2013 at 23:42

I think there might be a misunderstanding of what tissue transglutaminase (TTG) does. TTG is sold in the food industry as "meat glue"... it's an enzyme for sticking proteins together - specifically an amine and a glutamine.

I don't think this enzyme has anything to do with the digestive process. As I understand it, TTG is required to create physically stable cell structures, which is what you need if you're building new tissues in the body. TTG is found all over the body, not just in the gut.

They've shown that the interaction of TTG with gluten is part of the pathological process in celiac disease. TTG can stick the glutamine part of the gliadin molecule to other molecules, and when it releases it, the amine gets left behind, creating the "deamidated gluten peptide" (DGP). These DGP can trigger the immune response*.

*J Pediatr Gastroenterol Nutr. 2008 Mar;46(3):253-61. doi: 10.1097/MPG.0b013e31815ee555. Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize. http://www.ncbi.nlm.nih.gov/pubmed/18376241

It seems to me that damaged tissue is going to create a lot more TTG as it tries to repair itself, and if the gluten reacting with the TTG is adding to the damage, then the situation can run away with itself.

What I don't understand is where the process starts. I reckon that poor digestion is a part of the story, so that more gluten arrives intact in the small intestine, but I also think there is likely to be a factor that allows the TTG and the gluten to get together... maybe the gut barrier breaks down in some way due to dysbiosis.

Whatever is happening, I reckon that in someone with a healthy digestion the TTG and the gluten/gliadin would never be able to meet up.

This doesn't answer your original question, Melissa, but I write it to dispute your argument that TTG is for digesting gluten. It's not.

  • I don't think TTG is for digesting gluten and I didn't write that I thought that. It has many roles. But does it play a role in breaking gluten down at all? That's what I wrote- that they are enzymes in the body that break down gluten.
    – Melissa
    Mar 8, 2014 at 21:08
  • You're right, you didn't explicitly say TTG digests gluten, but you did say "So it's an enzyme that normally breaks down gluten and the process has gone haywire". In a healthy person, I don't think it's normal for TTG and gluten to get together at all - and when TTG and gluten do get together, this fuels the celiac disease process.
    – poing
    Mar 10, 2014 at 11:47

I see problem that most of (digestibility) studies are in vitro, likely analyzing pure protein alone, not whole product and its preparation like cooking/baking that decreases the digestibility sometimes.


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