Microbial Biomarkers in Patients with Nonresponsive Celiac Disease

Abstract

Background and Aims In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD. Methods ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls. Results At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79). Conclusions Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.

First-degree Relatives of Celiac Disease Patients Have Increased Seroreactivity to Serum Microbial Markers

“…ASCA is known to cross-react with other yeast strains [49], and the lack of correlation between ASCA antibodies and Saccharomyces cerevisiae DNA on intestinal mucosa [50] indicates the possibility of some yet-unidentified cross-reactive antigens. In accord with our previous study [51], for currently unclear reasons, ASCA levels were generally higher in the IgG class than the IgA class. By contrast, IgA class ASCA seems to be more consistently elevated in IBD [48,52].…”

Gut Microbiome of a Multiethnic Community Possessed No Predominant Microbiota

“…The dominating microbiota Bacteroides in Cluster 1 has been aligned with health benefits described in the Introduction; however, it is also listed as an independent highrisk factor for many common diseases in developed countries. These include arterial diseases [32,33], type-2 diabetes [34,35], colorectal cancer [36][37][38], cardiomyopathy [39], rheumatoid arthritis [40], inflammatory bowel disease [41], Parkinson's disease [42], celiac disease [43] and Alzheimer disease [44]. On the other hand, Cluster 2 microbiome is dominated by Prevotella.…”

T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease

“…However, as the majority of CeD patients in these studies did not have evidence of prior viral exposure, other triggers for CeD development are likely. A range of studies now support a secondary role for opportunistic bacterial pathogens in CeD 18,[29][30][31][32][33][34][35][36][37] . Proteases from commensal gut bacteria are capable of degrading gluten proteins and releasing immunogenic peptide fragments more amenable to absorption, and can directly exacerbate gluten immunopathology in a HLA-DQ8 mouse model 36,37 .…”