Celiac disease is characterized by an intolerance of gluten, a protein that is widely present in our diet and notably in certain cereals such as wheat. Patients who suffer from this disease need to follow a strict and restrictive diet designed to exclude gluten and thus improve their symptoms. Several factors are involved in triggering this disease and they are notably genetic and immune. Because the disease is characterized by inflammation of the gut, the scientists started to look at the role of the gut microbiota already several years ago. Already in 2015 it wa demonstrated that coeliac children had an unbalanced composition of some gut community species and lacking of some Lactobacillus strains. These seem important for digensting gluten: they possess indeed some proteases able to cleave peptide bonds in gluten that are resistant to conventional proteolysis in human digestive system. Moreover, the administration of lactobacilli as a supplement in coeliac kids, reduces the production of TNF-alpha, a cytotoxic cytokine responsible for the flattening of intestinal villi in gut mucosa, a feature in coeliac disease.
For this reason, some clinical trials already investigated the beneficial effeects of probiotic supplementation in this condition. Either Lactobacillus and Bifidobacterium strains were tested. Very recently, othe commensal strains in the gut or the the mouth were identified a salso potentially ale to hydrolize gluten peptides responsible for the progression of the disease, like Rothia aeria and Bacillus tiquelensis. Beside probiotics, however, diet in coeliac disease is important to maintain health beside the gut or muscle wellbeing. Gluten-free products are incomplete from a nutritional point of view; they are enriched in carbohydrates and the protein content, instead, is poor with essential aminoacids like lysine, phenylalanine and tryptophan. Some Authors have suspected that, beside malabsorption, a lower protein quality in coeliac patients might lead, in time, to a weakening of certain functions in nervous sytem and predispose to conditions like depression. Indeed, neurotransmitters like dopamine and serotonin, which are deficient in depression, are derived from the aforementioned aminoacids.
In healthy subjects, moreove, some bacteria in the microbiota specifically utilize tryptophan (an amino acid found in the diet) to produce compounds called indole derivatives that activate transcription factor AhR (Aryl hydrocarbon Receptor) present in immune cells and on gut mucosa cells. Activation of these receptors generates beneficial effects such as reinforcing the intestinal barrier or stimulating immunity, which then attenuate gut inflammation and preserve the balance of the gut microbiota. In other inflammatory intestinal diseases (Crohn’s disease and ulcerative colitis) scientists had previously demonstrated changes to the microbiota, and particularly a defect in the production of these tryptophan derivatives and hence a reduction in AhR activation. Very recently, an international research consortium involving teams from McMaster University, INRAE, Sorbonne University Paris, INSERM, Paris Public Hospitals and Wageningen University (Netherlands) has shown that the intestinal microbiota of celiac patients displays a defect in the production of active tryptophan metabolites by microorganisms.
Their showed that a dietary intake of tryptophan or supplementation with probiotics that can metabolize this amino acid diminish the intestinal lesions of celiac disease in animals and offer new therapeutic prospects in humans. The scientists analyzed stool samples from a cohort of 29 patients – who were either suffering from active celiac disease or had the disease and had been treated for 2 years with a gluten-free diet – and from healthy volunteers without celiac disease. Their results revealed that in patients with active celiac disease it was only possible to detect a reduced quantity of tryptophan indole derivatives and a diminished activation of AhR. As well as inflammation, the team also observed changes to the intestinal microbiota which resulted in fewer microorganisms metabolizing tryptophan and producing the indole derivatives (scatole, indoleacetic and indole-propionic acids) necessary to activate AhR. In model mice developing a condition similar to celiac disease, the scientists modulated the diet in two ways: they either administered an additional intake of or they gave them the probiotic bacterium Lactobacillus reuteri which produces indole derivatives from tryptophan.
When the mice were exposed to gluten, the intestinal inflammation of those given a tryptophan-enriched diet was reduced when compared to those receiving a standard diet. The same results were observed among rodents which received the Lactobacillus reuteri probiotic. In addition, the tryptophan-enriched diet or the probiotic bacterium enabled significant improvements to the celiac disease lesions in mice when they were exposed to gluten. It is worthy remember that this aminoacid can be esaily foind in good amount in foods like meat, liver, poultry, fish, dairy products, dried fruits, soy derivatives, etc.). However, it seems that other aminoacids are lower in the plasma of coeliac individuals, even in children. Cysteine and glutamine are among these. Bread gluten is extremely rich in aminoacids like proline, glutamine, cysteine and glicine. None of them is essential but they play a pivotal role in intermediate metabolism. Gluten-free foods like bakery are based on maize and rice, which cointain a good amount of the aforelisted aminoacids. Nonetheless, investigations have proved that some prolamins and prolamin-like proteins in these cereals are resistant to regular digestion in the human gut.
This situation is enhanced in case of coeliac disease. From one side, digestion is impaired by pancreatic exocrine impairment due to the chronic condition and the excessive carbohydrate load; on the other hand, mucosal villi flattening prevent the regular absorption of aminoacids, vitamins and other nutritional principles. The situation is, in addition, worsen by the dysbiotc condition. Villi are the resident place for the regular gut microbiota communities; once lost by chronic inflammation, the resident flora gets lost as well. Therefore, uprooting the chronic inflammation in coeliac disease is the first step to enhance villi regeneration. The next step is to allow microbiota to expand again through either supplementation and/or prebiotics. Nutritional enhancements through aminoacids or selected proteins, finally, would restore the former shortage of metabolites that are needed to keep an acceptable health status in those affected by the condition.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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