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Gut microbiota as a new player in children with celiac disease

Celiac disease (CD), historically defined as an immune‐mediated enteropathy triggered by the ingestion of dietary gluten, has a substantial increase in prevalence and diagnosis rate globally. Indeed, patients with CD are often undetected and are exposed to the risk of long‐term complications, resulting in substantially increased burden of CD, which now emerges as a widespread issue of public health. Although the major known risk factors related to CD are common in China, recent studies indicated that CD is not rare in the general Chinese individuals as previously reported, which might be because manifestations of CD are relatively mild and indistinguishable with those of other chronic diseases, such as irritable bowel syndrome (IBS) or functional dyspepsia (FD). There is an increased awareness in the clinical practice of CD in China, with obviously cumulative information according to an extensive search on the public database. As the leading article by Wu et al. pushed their research work toward the Chinese population in 2010, CD is now emerging in China, demonstrated by serological screening, with higher frequency in CD subjects carrying HLA‐ DQ2/DQ8 genotypes, as well as in the Northern China where wheat was regarded as a staple food. As expected, the prevalence of CD among Chinese population varied from different regions, resulting in an underestimate of CD incidence in China. In addition, several other publications revealed that the prevalence of CD was variable among certain clinical patterns of high‐risk groups. Nevertheless, there is a lack of sufficient data about the comprehensive picture of CD in China, especially in the general population of young children. In general, CD could occur at any age, while majorly manifests at a very young age, with a peak incidence in children under 2 years. According to a cross‐sectional prospective study involving 19 778 adolescents and young adults in China, the prevalence of CD was approximately 2%, which is slightly higher than that around the world, owing to the increase of wheat consumption as well as HLA‐DQ2/DQ8 carriers in China these years. In addition to clinical symptoms of malabsorption, evidence from prospective studies also indicated that CD children might suffer from important health problems, including impaired growth, reduced bone mineral density, and increased risk of developing into inflammatory bowel disease (IBD) or lymphoma of gastrointestinal cancers. Delayed diagnosis of CD and the consequent prolonged period of dietary exposure to gluten might be correlated with high risk of cancer occurrence. In terms of management of CD, early prevention and intervention is beneficial for CD patients preventing serious complications or a malignancy. Thus, it is essential to clearly understand the experiences of individuals who suffer from CD and properly estimate the burden of CD in China. There are a number of children considered to have an increased risk of CD occurrence, such as those with family history of CD, those who carry a susceptible gene, or those suffering from other autoimmune diseases. Interestingly, nearly 30% of the general population carries HLA‐DQ2/DQ8 genes, but most of those subjects would not eventually progress into CD. Emerging evidence widely point out an increased risk of CD in children birth via cesarean delivery as compared to children born through vaginal delivery, due to alterations in neonatal gut flora associated with different birth delivery modes. Di Cagno et al. suggested that the composition of fecal microbiota in 19 CD children had significant differences compared with healthy individuals, mainly characterized by lower abundance of lactobacilli, enterococci, and bifidobacteria in CD children. Specifically, patients experiencing CD with gastrointestinal symptoms were dominated by Proteobacteria and lower microbial diversity, whereas the patients with dermatitis herpetiformis or dyspepsia were presented mainly with Firmicutes, which suggested that intestinal microbiota may play functional roles in the clinical manifestation of CD disease. In turn, it is reasonable to hypothesize that the imbalance of gut microbiota may associate with the pathogenesis and the clinical course of CD. The human gastrointestinal tract harbors a plethora of microorganisms. Indeed, healthy subjects prevent bacteria penetration and systemic dissemination via maintaining the integrity of intestinal barrier and the diversity of gut flora, whereas CD is characterized by an impaired intestinal barrier resulting in an increased intestinal permeability. Further, studies indicated that dysbiosis of gut microbiota would activate and shape T cell‐mediated immune response, to facilitate the gluten tolerance in genetically predisposed individuals with CD. Consequently, it is perceived that intestinal microbiota or its components would translocate into the circulation system and precede inflammation activation, ultimately leading to CD development. Nevertheless, the underlying mechanism of how dysbiosis of intestinal microbiota contributes to the early‐onset and altered clinical manifestations of CD in children remains unclear. The pilot study by Di Biase et al. in the present issue of Journal of Gastroenterology and Hepatology has aptly put attention to the gut microbiota patterns and clinical symptoms in CD children at onset. In this study, the authors attempted to interpret the potential association toward dysbiosis of gut microbiota and CD onset via comparing the microbiota composition of CD patients and healthy controls, in stool samples and duodenal mucosa, respectively. That is, the gut microbial signatures in children at CD onset have been delineated; similar to previous studies, the dominant gut microbiota of Enterobacteriaceae and subdominant component of Bacteroidetes/Streptococcus were abundant in the duodenal microbiota of CD patients, whereas a reduced amount of several microbiotas, including Bacteroides–Prevotella, Akkermansia, and Staphylococcaceae, were shown in the stool samples, compared with healthy controls. As regard to the relationship between CD clinical symptoms and microbiota composition, there is a pro‐inflammatory bacteria imbalance related to CD symptoms, which is different from that of healthy individuals. Collectively, this study suggested the correlation between gut microbiota dysbiosis and clinical symptoms at CD early onset. doi:10.1111/jgh.15322