What happens to gluten in the body?
Gluten is the name for certain types of proteins found in wheat, barley and rye grains. Proteins are long chains of amino acids that fold and bind to themselves and other amino acid chains via chemical bonds, forming three-dimensional structures. In order to be absorbed through the intestinal lining and used to fuel the body, proteins must be unfolded and broken down into short snips of no more than 2-3 amino acids. Enzymes in the body catalyze, or trigger, reactions that break the bonds that hold food components together during digestion.
Gluten proteins are rich in the amino acids proline, glutamine and cysteine, which humans don’t have the necessary enzymes to break down completely, making them particularly difficult for the human body to digest. This leaves gluten fragments intact in the digestive tract, where they interact with the immune system, intestinal lining and microbiome.
Gluten in the Mouth
Chewing manually breaks down proteins, allowing saliva and microbes in the mouth to have more access to the proteins. It was conventionally thought that there are no proteases, enzymes that break the links between amino acids, in saliva, where there are enzymes that break down carbohydrates and fats, but new research suggests that certain microbes in the oral cavity can produce proteases that break apart gluten proteins (Tian et al., 2017).
Gluten in the Stomach
Proteins are further broken apart by the churning action of mechanical digestion in the stomach. Muscles squeeze it in alternating waves so that the contents are turned and mashed, allowing the hydrochloric acid and enzymes produced by stomach cells to make contact with as much of the food as possible. Acid breaks the links that form protein structures, unfolding them so that pepsin, the stomach enzyme that breaks down proteins, can get to the links between amino acids. Pepsin mainly breaks links with phenylalanine, tyrosine and asparagine and, less preferentially, glutamine, and doesn’t break links with valine, alanine, or glycine (Heda et al., 2022).
Gluten in the Small Intestine
Once the stomach contents are liquified, they are squirted into the small intestine and mixed with proteases from the pancreas that are more specific to different links in the amino acid chain. The enzyme chymotrypsin cleaves bonds with phenylalanine, leucine, tryptophan and tyrosine. Trypsin breaks bonds with arginine and lysine, and elastase breaks down proteins at links with alanine, glycine and serine. Finally, carboxypeptidases chop off individual amino acids from the ends of the remaining chain fragments (Leiberman & Peet, 2018).
Large amounts of undigested gluten proteins persist in the upper small intestine, feeding certain microbes that can use them as fuel. Studies on patients with celiac disease show that this allows these microbes to to proliferate and can lead to dysbiosis (Bernardo et al., 2009).
Gluten in the Intestinal Lining
There are more enzymes in the brush border, projections of intestinal cells into the intestinal cavity that look like bristles of a brush, that keep breaking protein fragments into smaller chains. Once protein fragments are down to about 2-3 amino acids, they can be absorbed into intestinal cells, where they are finally broken into individual amino acids by proteases inside the cells. From there, amino acids pass through the cell membrane into the bloodstream (Leiberman & Peet, 2018).
However, all the protein-degrading enzymes that gluten passes through can’t digest it completely because of the high proline content of gluten chains. Links to proline are not easily reached by enzymes, leaving sections of amino acids, called gluten peptides, intact (Hausch et al., 2002).
Some of these peptides have sequences similar to opioids and can attach to opioid receptors in the gut. Called gluteomorphins or gluten exorphins, these peptides could account for the many cases of asymptomatic celiac disease, in which no abdominal pain or other classic celiac symptoms are present, but antibodies against gluten are found in blood tests (Manai et al., 2023).
Other gluten peptides attach to receptors on intestinal cells and trigger tight junctions, the spaces between cells, to open and allow them and other intestinal contents to pass through. Once through, the peptides interact with immune cells and cause an inflammatory response (Lammers, et al., 2008).
Some parts of these peptides are called epitopes, amino acid sequences that form a shape that antibodies produced by the immune system can attach to, as seen in gluten intolerance. Gluten proteins can form at least 50 different epitopes that aren’t degraded by gastrointestinal proteases (Wei et al., 2020).
Tissue transglutaminase (tTG) is an enzyme in the intestinal lining that can either connect two proteins via a glutamine-lysine bond, forming large gluten complexes, or convert glutamine to glutamic acid to make what is called deamidated gluten, a form of gluten that is even more reactive with the immune system (Ciccocioppo et al., 2003). Finally, tTG can bind itself to gluten peptides, forming a tTG-gliadin complex that leads to formation of anti-tTG antibodies, which are seen in celiac disease (Paolella et al., 2022).
Gluten in the Large Intestine
When undigested gluten peptides make their way to the large intestine, they are fed on by certain types of gut microbes that can digest the proteins, including Lactobacillus, Streptococcus and Clostridium species (Caminero et al., 2014). The amounts and balance of different types of microbes, some of which have positive effects in the body and some negative, both affect and are affected by the presence of gluten peptides. Reaction to gluten causes the immune system to emit chemicals that alter gut microbial composition, and ingestion of gluten causes an increase in microbial species that feed on gluten peptides. Studies show that celiac patients who eat gluten have higher amounts of Proteobacteria and lower amounts of Firmicutes and Actinobacteria compared to those on the gluten-free diet or those without celiac disease (Wu et al., 2021).
Finally, stool samples show that some gluten particles make it through the entire digestive tract intact, including epitopes that trigger immune responses (Comino et al., 2012).
References
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