The Role of Early Programming and Early Nutrition on the Development and Progression of Celiac Disease: A Review

Abstract

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or fetal programming. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including celiac disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age of gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1–3%. It is not known what factors act to modify the risk of disease in genetically at-risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD. It is logical that attention has been paid to gluten as a key element in preventing the disease. However, there is no strong evidence in favor of the protective factor of breastfeeding, timing of introduction of gluten during lactation, and the development of CD. Diet, genetic risk, microbiota, and environmental interaction are possible triggers of the change in tolerance to an immune response to gluten, but large-scale cohort studies are needed. Emerging scientific concepts, such as epigenetics, may help us establish the role of these factors.

Fetal-maternal interactions with gluten immunogenic peptides during pregnancy: a new determinant on the coeliac exposome

“…The individuals with Down syndrome have a higher predisposition to autoimmune diseases (2, 37), including CD (38). The up regulation of a panel of proteins and their potential as a biomarker for prenatal diagnosis and as revealing of pathogenesis of Down syndrome has also been demonstrated (39).…”

“…The notable increase in the incidence of gastrointestinal (GI) pathologies has led to the search for a deeper understanding of the role of the GI immune system. There has been interest in the ontogeny, early growth, and development of the intestine during the prenatal stages because of its potential to play a role in gut physiology or pathological challenges in later life (1)(2)(3). Ontogenesis of the immune system begins as early as 3 weeks after conception and continues after birth and childhood (4).…”

Making Research Flourish Through ESPGHAN

“…Although the incidence and prevalence of CD have increased quite dramatically over the last decades, this cannot be explained by increased awareness alone (35). So far, several environmental factors have been investigated, such as the effects of early nutrition, the presence of a typical microbiota in celiac patients and antibiotic exposure in early life (37). Also, while in various genome‐wide association studies (GWAS) up to 40 non‐HLA loci have been identified as potentially related to CD (38), the effect was proven very weak.…”

Consensus Weighted Gene Co-expression Network Analysis demonstrates aberrations in folding of actin by CCT/TriC chaperonin family in Celiac disease

“…The entry of gluten into the small intestine leads to painful digestive disorders, followed by in ammation of the intestinal mucosa, villous atrophy, and crypt hyperplasia (3). As a complex disease, celiac is caused by a combination of genetic and environmental factors (4). The main genetic susceptibility factors for CeD are human leukocyte antigen (HLA)-DQ2 and -DQ8 haplotypes, which account for approximately 40% of the heritability of celiac disease (5,6).…”