Establishment of microbial biomarkers in non-responding celiac disease patients.

Introduction: Celiac disease (CeD) is an autoimmune disease affecting the small intestine due to gluten consumption. The treatment involves adherence to a gluten-free diet (GFD); however, up to 30% of patients show symptoms after one year on a GFD, presenting non-responsive CeD (NR-CeD).  Evidence suggests that the microbiome plays a role in CeD progression and symptoms manifestations. Here we study the association of microbiome profiles with the persistence of symptoms in NR-CeD.

Methods: We performed shotgun metagenomics to stool samples of NR-CeD patients (n=40). We integrate the results with public data from healthy controls (n=37) and patients with CeD undergoing GFD (n=52). We performed an analysis combining the datasets, calculated diversity indexes, and performed a Linear discriminant analysis integrated with effect size (LEfSe) to find microbial biomarkers of each condition. 

Results: We found that the microbiome of NR-CeD was less diverse than healthy controls and R-CeD (Table). After LEfSe analysis (Figure) we found that the microbiome from healthy controls was dominated by bacteria from the phylum Firmicutes and Actinobacteria (i.e:  f_Ruminocacceae, g_Bifidobacterium,). The R-CeD microbiome was characterised by bacteria from the phylum Proteobacteria, Verrucomicrobia, and Firmicutes (c_Clostridia, c_Negativicutes). NR-CeD microbiome was enriched in bacteria from the phylum Bacteroidetes (o_Bacteroidales), and Firmicutes (c_Clostridia).

Conclusion: CeD patients under prolonged treatment shift their microbiome differently than healthy controls and NR-CeD, suggesting specific microbial changes associated with symptoms prevalence. Moreover, we found microbial biomarkers associated with NR-CeD, mainly genus related to active CeD in the literature (Bacteroides spp.)