Microbiome and Gluten

Abstract

Celiac disease (CD) is a frequent chronic inflammatory enteropathy caused by gluten in genetically predisposed individuals that carry disease susceptibility genes (HLA-DQ2/8). These genes are present in about 30-40% of the general population, but only a small percentage of carriers develops CD. Gluten is the key environmental trigger of CD, but its intake does not fully explain disease onset; indeed, an increased number of cases experience gluten intolerance in late adulthood after many years of gluten exposure. Consequently, additional environmental factors seem to be involved in CD. Epidemiological studies indicate that common perinatal and early postnatal factors influence both CD risk and intestinal microbiota structure. Prospective studies in healthy infants at risk of developing CD also reveal that the HLA-DQ genotype, in conjunction with other environmental factors, influences the microbiota composition. Furthermore, CD patients have imbalances in the intestinal microbiota (dysbiosis), which are not fully normalized despite their adherence to a gluten-free diet. Therefore, it is hypothesized that the disease can promote dysbiosis that aggravates CD pathogenesis, and dysbiosis, in turn, can initiate and sustain inflammation through the expansion of proinflammatory pathobionts and decline of anti-inflammatory mutualistic bacteria. Studies in experimental models are also contributing to understand the role of intestinal bacteria and its interactions with a predisposed genotype in promoting CD. Advances in this area could aid in the development of microbiome-informed intervention strategies that optimize the partnership between the gut microbiota and host immunity for improving CD management.

Infection’s Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility

“…Differences in microbiota composition and resilience may also explain the numerous diseases associated with secretor status (as detailed in Table 1). Many of these conditions (including asthma, Crohn's disease, celiac disease, and psoriasis) are associated with intestinal microbiota composition [48][49][50]. If secretor status can influence gut microbiology, it is reasonable to suggest that secretor status may contribute to microbiota-related disease susceptibility among predisposed individuals, as discussed elsewhere [8,30,31,46,[51][52][53].…”

The human digestive tract has proteases capable of gluten hydrolysis

“…The pathogenesis of CD involves genetic and environmental factors. Susceptibility to CD is strongly associated with the human leukocyte antigen (HLA) genes of the major histocompatibility complex, and approximately 90% of patients express alleles coding for the HLA-DQ2 (HLA-DQ2.5 and HLA-DQ2.2) and HLA-DQ8 haplotypes [1], [4], [5]. The diet is the fundamental factor contributing to the development of CD.…”

Metagenomics approach to the study of the gut microbiome structure and function in zebrafish Danio rerio fed with gluten formulated diet

“…Wheat gluten is comprised of the water soluble monomeric protein gliadin, and insoluble multimeric glutenin, and is immunostimulatory to patients with genetically predisposed celiac disease (CD), and the etiologic agent of non-celiac gluten sensitivity (NCGS) (Howdle, 2006; Narrowe et al, 2015; Sanz, 2015). The pathophysiology of CD has been extensively probed, of which gluten induced autoimmune responses manifest aberrant intestinal mucosa conditions, characterized by inflammation and lesions, leading to malabsorption at the site of immune response followed by diarrhea and steatorrhea (Murray, 1999; Van Kessel et al, 2011).…”

“…For NCGS, despite a reported ~6% of the human population affected, little is known of the factors underlying and/or progressing enteropathy, beyond the involvement of gluten (Elli et al, 2015; Sapone et al, 2012). Both CD and NCGS have received attention regarding population shifts and perturbations in intestinal bacteria (microbiota) that may be directly or indirectly correlated with disease states (A Daulatzai, 2015; Lotta et al, 2016; Samsel and Seneff, 2013; Sanz, 2015). Examinations of the microbiota of patients with CD and NCGS have concluded similar increases of harmful gram-negative bacteria, pathobionts and overall microbial dysbiosis (A Daulatzai, 2015; Béres et al, 2014 ).…”