Tag: gluten

Categories : Allergies Diet and NutritionTags :

Celiac Disease: New Findings on the Effects of Gluten

On By ModernMedia
Photo by Mariana Kurnyk

May 16 is International Celiac Day. Celiac disease is a chronic autoimmune condition that occurs in around 1% of the world’s population. It is triggered by the consumption of gluten proteins from wheat, barley, rye and some oats. A gluten-free diet protects celiac patients from severe intestinal damage. Together with colleagues, chemist Dr Veronica Dodero from Bielefeld University was able to determine new details on how certain gluten-derived molecules trigger leaky gut syndrome in celiac disease.

The key finding of the study: a particular protein fragment formed in active celiac disease forms nanosized structures, the so-called oligomers, and accumulates in a gut epithelial cell model. The technical name of the molecule is 33-mer deamidated gliadin peptide (DGP). The study team has now discovered that the presence of DGP oligomers may open the tightly closed gut lining, leading to the leaky gut syndrome. The study has now been published in the journal Angewandte Chemie.

Wheat peptides causing leaky gut

Gluten proteins cannot be completely broken down by the gut. This can lead to the formation of large gluten fragments (peptides) in our gut. In cases of active coeliac disease, researchers discovered that the enzyme tissue transglutaminase 2 (tTG2) present in humans modifies a specific gluten peptide, resulting in the formation of the 33-mer DGP. This usually happens in a part of our gut called the lamina propria. However, recent research has shown that this process can also occur in the gut lining.

‘Our interdisciplinary team characterized the formation of 33-mer DGP oligomers through high-resolution microscopy and biophysical techniques. We discovered the increased permeability in a gut cell model when DGP accumulates, reports Dr. Maria Georgina Herrera, the first author of the study. She is researcher at the University of Buenos Aires in Argentina and was a postdoctoral fellow at Bielefeld.

When the intestinal barrier is weakened

Leaky gut syndrome occurs when the lining of the intestine becomes permeable, allowing harmful substances to enter the bloodstream, leading to inflammatory responses and different diseases. In celiac disease, there’s debate about the early stages of increased permeability. The mainstream theory suggests that chronic inflammation in coeliac disease leads to a leaky gut. However, there is a second theory that proposes that gluten’s effects on gut lining cells are the primary cause. In this view, gluten directly damages the cells of the intestinal lining, making them permeable, which triggers chronic inflammation and potentially leads to celiac disease in predisposed people.

However, since gluten is consumed daily, what molecular triggers lead to the leaky gut in celiac disease patients? If 33-merDGP oligomers are formed, they may damage the epithelial cell network, allowing gluten peptides, bacteria, and other toxins to pass massively into the bloodstream, leading to inflammation and, in celiac disease, autoimmunity.

‘Our findings reinforce the medical hypothesis that impairment of the epithelial barrier promoted by gluten peptides is a cause and not a result of the immune response in celiac patients,’ says the lead author of the study, Dr Veronica Dodero from the Bielefeld Faculty of Chemistry.

The relationship between 33-mer DGP and Celiac Disease

Human leukocyte antigens (HLAs) are proteins found on the surface of cells in the body. They play a crucial role in the immune system by helping it distinguish between self (the body’s own cells) and non-self (foreign substances like bacteria or viruses). In celiac disease, two specific HLA proteins, namely HLA-DQ2 and HLA-DQ8, are strongly associated with the condition. The 33-mer DGP fits perfectly with HLA-DQ2 or HLA-DQ8 and triggers an immune response, leading to inflammation and small intestine villous atrophy. This strong interaction turns the DGP into what scientists call a superantigen. For those affected, a gluten-free diet is the only lifelong therapy.

Source: Bielefeld University

Categories : Diet and NutritionTags :

People with Gluten Sensitivity have Negative Effects – Even When Eating a Placebo

On By ModernMedia
Photo by Mariana Kurnyk

Symptoms of gluten sensitivity are partly to do with people’s expectations, if celiac disease and wheat allergy have been excluded as causes. Recent research at the universities of Maastricht and Leeds shows that the expectation that gluten causes gastrointestinal complaints plays a crucial role in whether or not people experience these symptoms. These results, published in The Lancet Gastroenterology and Hepatology, indicate a direct involvement of the interaction between the brain and the intestines – the ‘gut-brain axis’ – in the experience of complaints after ingesting gluten.

Fear of gluten

A growing number of people are reducing their gluten intake due to self-reported digestive complaints, despite the fact that celiac disease and wheat allergy have been ruled out. The cause of their symptoms is often unclear. The researchers therefore wanted to investigate the effects of expectations on symptoms experienced after gluten intake. More than 80 subjects with self-reported gluten sensitivity took part in a psychological study and were divided into four groups. The results were unequivocal: people who thought they were eating food containing gluten reported more symptoms, while those who thought their food was gluten-free reported fewer symptoms.

In reality, the food given to half of each group contained gluten, while for the other half it was gluten-free. In all of the groups people’s expectations played a prominent role in whether or not they reported symptoms after eating. “In our research, we see a so-called nocebo effect when people eat gluten,” says researcher Marlijne de Graaf. “If people expect gluten to produce negative effects, they experience symptoms, even if it turns out afterwards that they weren’t actually eating gluten. Although the cause is partly ‘in the mind’, this doesn’t mean that the symptoms are not real.”

Gut-brain axis

The results of this study indicate a clear involvement of the interaction between the brain and the intestines in gluten sensitivity, a subject on which knowledge is as yet limited. The researchers therefore now want to concentrate on unravelling the mechanisms that determine the importance of expectation and exposure along the gut-brain axis. ‘Due to the influence of interactions between the brain and the intestines, people can genuinely experience symptoms such as stomach ache, bloating or diarrhoea after eating gluten,’ says Daisy Jonkers, professor of Intestinal Health at Maastricht University. ‘But the cause of these complaints is not only eating gluten, so a gluten-free diet isn’t the only solution.’

To treat this problem, the researchers want to conduct further studies on the influence of the brain on the development of bowel complaints. ‘For example, we’d like to know exactly which areas in the brain are involved,” says Jonkers, “and we also want to find out what substances play a role in the communication between the brain and the gut, and whether people might respond differently to them. It’s also quite possible that some people can’t tolerate wheat products because of substances in wheat other than gluten, and that there is indeed something in wheat that can lead to overstimulation of the immune system, for example, or excessive production of gas by the gut flora. This is also something we’d like to investigate.”

Source: Maastricht University