Gluten and intestinal inflammation

gluten induces intestinal inflammation not only in celiac individuals but also in healthy ones

Intestinal inflammation is a condition of the gastro-intestinal system that affects a very large and constantly increasing number of people (1). This condition represents for the individual not only a state of disconfort that affects the quality of life but can – if underestimated or neglected – promote the onset or aggravation of serious illnesses.
An important role but still to be fully explored is played by gluten as it is pro-inflammatory.
The study ” The Role of Gluten in Gastrointestinal Disorders: A Review. Sabrina Cenni. Gastrointestinal Disorders: A Review. Nutrients 2023” provides a useful overview of its effectiveness in the prevention and management of these disorderes.

“Abstract: Gluten is only partially digested by intestinal enzymes and can generate peptides that can
alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of intestinal inflammation and in other gastrointestinal disorders. The aim of this narrative review was to analyse the role of gluten in several gastrointestinal diseases so as to give a useful overview of its effectiveness in the prevention and management of these disorders.”

“Introduction. Gluten is a protein mass made of a complex network of gliadins and glutenins, which are proteins rich in glutamines and prolines found in most grains, such as barley, wheat, and rye [1 ,2]. Due to its high-water binding capacity and its consequent malleability and elasticity, gluten induces the formation of viscoelastic membranes, thus determining the proper consistency of dough, which allows it to be processed in bread and other foods [ 3– 5]. The high content of glutamines and prolines in gliadins make them difficult to cleave, making them able to escape degradation from gastric, pancreatic, and intestinal proteolytic enzymes [3, 4]. Therefore, gluten is what remains after the removal of starch, water-soluble proteins, and albumins [1]. In Western countries, the gluten dietary intake is approximately 5 to 20 g per day [3 , 4]. In the last decades, the literature reports an increased number of reactions following a widespread exposure to gluten [ 6]. Gluten-related diseases affect up to 10% of the general population and can be classified as three different disorders: IgE-mediated wheat allergy, Celiac disease (CD), and non-celiac gluten sensitivity (NCGS) [2, 6]. However, there is increasing evidence that gluten can trigger an innate and adaptative immune response responsible for intestinal inflammation [7]. Notably, along with other dietary elements, gluten may contribute to the development of inflammatory intestinal disorders, such as inflammatory bowel disease (IBD), as well as functional gastrointestinal disorders (FGIDs) and concur in symptom exacerbation, although its exact role is still under investigation.”

Gluten and intestinal inflammation. “Inflammation is the natural response of the innate immune system to external stimuli, such as microbial pathogens and injuries [8 ]. When the trigger persists and the immune cells are constantly activated, the inflammatory response may become chronic and self-sustainable [8]. The aetiology of inflammation is clear and easily detectable in some health conditions, while in others it can be difficult to identify [ 8]. The pathogenesis of inflammation is multifactorial. Nevertheless, genetic vulnerability, psychological stress, environmental factors, and some dietary patterns have been described as potentially implicated in the development of inflammatory phenotypes [ 8]. There are at least 50 different types of gliadin epitopes that can have an immunomodulatory and cytotoxic role or that can impact the gut permeating activities [ 8 ]; in fact, some of these can stimulate a pro-inflammatory innate immune response and others can activate specific T cells [8]. Gliadins immune cells’ activation is not only observed in celiac patients, as described by Lammers et al. [9, 10]. Indeed, their study concluded that gliadin induced an inflammatory response and, in particular, an important production of pro-inflammatory cytokines (IL-6, IL- 13, and interferon-gamma) both in Celiac patients and in healthy controls, even if proinflammatory cytokine levels were higher in Celiac patients [9, 10]. Similarly, Harris et al. showed that incubated peripheral blood mononuclear cells (PMBC) obtained from healthy HLA-DQ2 positive individuals produced proinflammatory cytokines, such as IL-23, IL-1beta, and TNF-α, when exposed to gliadin peptides [ 8, 11]. These cytokines’ production was significantly higher in Celiac patients compared to healthy controls [8,11]. Accordingly, Cinova et al., in their case-control study, demonstrated that gliadin could stimulate a substantial TNF-α and IL-8 production by monocytes, principally in celiac patients, but also, to a lesser extent, in healthy control individuals [12]. Gliadin also has an important role in modifying intestinal permeability through the reorganization of actin filaments and the modified expression of junctional complex proteins [ 8,13 ]. As demonstrated by Drago et al. and Lammers et al., gliadin’s binding to the chemokine receptor CXCR3 determines a release of zonulin, an active protein, which compromises the integrity of the intestinal barrier through the rearrangements of actin filaments, ultimately leading to an altered intestinal permeability both in Celiac and non-Celiac patients [ 9, 10, 14 ]. In conclusion, Ziegler et al. and Junker et al. reported that amylase trypsin inhibitors, found in gluten-containing cereals, have the capacity to activate toll-like receptors, thus stimulating the release of inflammatory cytokines and inducing a T-cell immune response in both celiac and non-celiac patients [15,16]”.

Einkorn wheat is the exception in relation to gluten-induced intestinal inflammation

A – Einkorn bread evidenced an anti-inflammatory effect. Integrated Evaluation of the Potential Health Benefits of Einkorn-Based Breads A. Gobetti et al. 2017.

B – Protective effects of ID331 Triticum monococcum. Protective effects of ID331 Triticum monococcum gliadin on in vitro models of the intestinal epithelium. Giuseppe Iacomino et al. (PMID: 27374565 DOI: 10.1016/j.foodchem.2016.06.014 ).

Keywords: gluten; inflammatory bowel disease; functional gastrointestinal disorders; celiac disease

Note

1 – Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9–40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2–21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6–1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3–1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Ami D. Sperber et al. Gastroenterology 2021;160:99–114