April 21, 2016
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N. flavescens abundant in duodenal biopsies of active celiac patients

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Microbiome analysis of duodenal biopsies from adults with active celiac disease revealed significant dysbiosis and an increased abundance of a “peculiar” bacterial strain called Neisseria flavescens.

“The aim of this study was to use 16S ribosomal RNA (rRNA) metagenomics to determine the [celiac disease]-associated duodenal dysbiosis in adult celiac patients and elucidate the mechanisms by which gut [celiac disease]-associated dysbiosis could concur to [celiac disease] development or exacerbation,” the researchers wrote.

They analyzed the microbiomes of duodenal biopsy samples from 20 adults with active celiac disease, six patients with celiac disease on a gluten-free diet, and 15 controls recruited from two academic centers in Italy. They then used isolated bacterial species to infect CaCo-2 cells and stimulate normal duodenal explants and cultured human and murine dendritic cells. They also assessed inflammatory markers using immunofluorescence and cytokines using enzyme-linked immunosorbent assay.

Proteobacteria was found to be the most abundant phylum in all three study groups’ biopsy samples, whereas Firmicutes and Actinobacteria were less abundant in the samples from patients with active celiac disease vs. the other two groups.

“Within the Proteobacteria phylum, the Betaproteobacteria class was highly represented in the gut microbiome of active [celiac disease] patients, although its levels did not directly correlate with disease severity,” the researchers wrote. “In addition, within the Betaproteobacteria class, the Neisseriales order (P = .009), the Neisseriaceae family (P = .01), and the Neisseria genus (P = .03) were significantly more abundant in active [celiac disease] patients than in the other two study groups, and the Neisseria genus was the most abundant genus (99.8%) within the Neisseriaceae family (P < .05).” Neisseria flavescens was the most abundant Neisseria species in the duodenal biopsies of patients with active celiac disease.

Whole-genome sequencing of Neisseria flavescens isolated from patients with active celiac disease compared with Neisseria flavescens isolated from controls revealed genetic differences in iron acquisition systems and in some genes related to hemoglobin. Moreover, the Neisseria flavescens isolated from patients with active celiac disease escaped the lysosomal compartment in CaCo-2 cells, and also induced inflammatory responses in dendritic cells and in ex vivo mucosal explants.

“In conclusion, marked dysbiosis and an abundance of a peculiar CD-Nf strain characterize the duodenal microbiome of active [celiac disease] patients, which suggests that the [celiac disease]-associated microbiota could contribute to the many inflammatory signals in this disorder.” – by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.