Dietary Gluten as a Conditioning Factor of the Gut Microbiota in Celiac Disease

Abstract

The gut microbiota plays a relevant role in determining an individual's health status, and the diet is a major factor in modulating the composition and function of gut microbiota. Gluten constitutes an essential dietary component in Western societies and is the environmental trigger of celiac disease. The presence/absence of gluten in the diet can change the diversity and proportions of the microbial communities constituting the gut microbiota. There is an intimate relation between gluten metabolism and celiac disease pathophysiology and gut microbiota; their interrelation defines intestinal health and homeostasis. Environmental factors modify the intestinal microbiota and, in turn, its changes modulate the mucosal and immune responses. Current evidence from studies of young and adult patients with celiac disease increasingly supports that dysbiosis (i.e., compositional and functional alterations of the gut microbiome) is present in celiac disease, but to what extent this is a cause or consequence of the disease and whether the different intestinal diseases (celiac disease, ulcerative colitis, Crohn disease) have specific change patterns is not yet clear. The use of bacterial-origin enzymes that help completion of gluten digestion is of interest because of the potential application as coadjuvant in the current treatment of celiac disease. In this narrative review, we address the current knowledge on the complex interaction between gluten digestion and metabolism, celiac disease, and the intestinal microbiota.

Keywords: celiac disease; gluten; gluten-free diet; gut; microbiota.

FIGURE 1

Digestion of gluten and food proteins. The digestion of food proteins, a fundamental substrate for human nutrition, is a metabolic process that takes place initially at the level of the stomach, where pepsin (a digestive endopeptidase) acts by promoting degradation of the original protein in polypeptides and amino acids. Then, these components follow further digestion at the level of the small intestine, where the digestion of food proteins is particularly important. It is here that enzymes from the pancreas, the striated border, and also some cytoplasmic enzymes, continue to digest dietary proteins up to tripeptides, dipeptides, and amino acids, and to optimize the absorption of proteins. The gluten protein shows peculiarities in its amino acid structure. Its amino acid content is composed of an important fraction of glutamine and proline residues, which have a fundamental role in protection of peptides against human proteolytic degradation. Proline-glutamine-rich epitopes are exceptionally resistant to enzymatic processing. Therefore, incompletely digested gluten protein and resulting peptides accumulate in the gastrointestinal tract. These protein fractions have antigenic capacity and can trigger autoimmune processes as characteristic of celiac disease. They can also become a substrate for bacteria that are part of the commensal or opportunistic microbiota at the oral or intestinal level, an interaction that can promote or reduce the antigenicity of these peptides. This figure was produced using “Servier Medical Art” from https://smart.servier.com.