Gut microbiota predicts the diagnosis of celiac disease in Saudi children

Abstract

BACKGROUND Celiac disease (CeD) is a multisystem immune-mediated multifactorial condition strongly associated with the intestinal microbiota. AIM To evaluate the predictive power of the gut microbiota in the diagnosis of CeD and to search for important taxa that may help to distinguish CeD patients from controls. METHODS Microbial DNA from bacteria, viruses, and fungi, was isolated from mucosal and fecal samples of 40 children with CeD and 39 controls. All samples were sequenced using the HiSeq platform, the data were analyzed, and abundance and diversities were assessed. For this analysis, the predictive power of the microbiota was evaluated by calculating the area under the curve (AUC) using data for the entire microbiome. The Kruskal-Wallis test was used to evaluate the significance of the difference between AUCs. The Boruta logarithm, a wrapper built around the random forest classification algorithm, was used to identify important bacterial biomarkers for CeD. RESULTS In fecal samples, AUCs for bacterial, viral, and fungal microbiota were 52%, 58%, and 67.7% respectively, suggesting weak performance in predicting CeD. However, the combination of fecal bacteria and viruses showed a higher AUC of 81.8 %, indicating stronger predictive power in the diagnosis of CeD. In mucosal samples, AUCs for bacterial, viral, and fungal microbiota were 81.2%, 58.6%, and 35%, respectively, indicating that mucosal bacteria alone had the highest predictive power. Two bacteria, Bacteroides intestinalis and Burkholderiales bacterium 1-1-47 , in fecal samples and one virus, Human_endogenous _retrovirus_K , in mucosal samples are predicted to be “important” biomarkers, differentiating celiac from nonceliac disease groups. Bacteroides intestinalis is known to degrade complex arabinoxylans and xylan which have a protective role in the intestinal mucosa. Similarly, several Burkholderiales species have been reported to produce peptidases that hydrolyze gluten peptides, with the potential to reduce the gluten content of food. Finally, a role for Human_endogenous _retrovirus_K in immune-mediated disease such as CeD has been reported. CONCLUSION The excellent predictive power of the combination of the fecal bacterial and viral microbiota with mucosal bacteria alone indicates a potential role in the diagnosis of difficult cases of CeD. Bacteroides intestinalis and Burkholderiales bacterium 1-1-47 , which were found to be deficient in CeD, have a potential protective role in the development of prophylactic modalities. Further studies on the role of the microbiota in general and Human_endogenous _retrovirus_K in particular are needed.

Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease—A Narrative Review

“…A group of researchers that evaluated the predictive power of fecal microbial dysbiosis in CD diagnosis reported that a combination of viruses and bacteria indicated an important predictive power in CD diagnosis, whereas, in mucosal samples, the strongest predictive power was obtained when the bacterial communities were analyzed alone. Compared to healthy controls' microbiota composition, CD patients could be identified by the reduction in Burkholderiales bacterium 1-1-47 and Bacteroides intestinalis levels in their fecal samples, or by Human endogenous retrovirus K in their duodenal mucosa specimens [51]. The reduced abundance of the two bacteria, with roles in degrading dietary fibers and reducing the gluten content of aliments, could be used to generate new therapeutic strategies [46].…”

The Contribution of the Intestinal Microbiota to the Celiac Disease Pathogenesis along with the Effectiveness of Probiotic Therapy

“…Comparison of the composition and functional activity of bacterial communities in patients with celiac disease and healthy volunteers makes it possible to better understand the contribution of microorganisms to the development of the disease. In the case of celiac disease, changes in the composition of the microbiota are observed: the proportion of Bacteroidetes and Proteobacteria increases, and the content of Lactobacillus, Bifidobacterium and Faecalibacterium prausnitzii decreases [50,[64][65][66][67][68][69]. Differences in the composition of Lactobacillus were found in children with celiac disease (predominance of L. curvatus) as compared to healthy children (L. casei, L. paracasei, L. rhamnosus, L. zeae).…”