Published online Apr 7, 2023. doi: 10.3748/wjg.v29.i13.1994
Peer-review started: November 2, 2022
First decision: December 11, 2022
Revised: December 29, 2022
Accepted: March 20, 2023
Article in press: March 20, 2023
Published online: April 7, 2023
Celiac disease (CeD) is a multisystem immune-mediated multifactorial condition strongly associated with the intestinal microbiota.
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.
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.
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.
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.
Core Tip: Celiac disease (CeD) is known to be associated with the microbiota. In this study, the combination of bacterial and viral taxa in stools and mucosal bacterial taxa were the strongest predictors of celiac disease. In addition, we report important bacterial markers, namely, Bacteroides intestinalis and Burkholderiales bacterium 1-1-47, which were reduced in children with CeD, suggesting a protective role in children with CeD.