Background/Purpose: Aortitis may occur in the context of multifocal large and medium-sized vessel diseases such as giant cell arteritis (GCA) or Takayasu arteritis (TAK) and as an isolated focal finding (focal idiopathic aortitis, FIA). In each setting, the aortic root and arch are the most common locations for aortic injury that is presumed to be autoimmune. It is not clear whether the propensity to affect the proximal aorta in these diseases suggests common pathways in pathogenesis that could include infection, abnormalities in immune tolerance or response, presence of neo-antigens, or alterations in substrate microbiome. A better understanding of disease pathogenesis may lead to new therapies and improved outcomes. Thus, we sought to describe the microbiome of inflammatory and non-inflammatory thoracic aortic aneurysms (TAA).

Methods: Patients with TAA who underwent surgical reconstruction were prospectively enrolled over a period of 3 years. TAA specimens were sterilely collected and snap frozen. Clinicopathologic data were gathered on all patients. Patients who had histologic evidence of inflamed aortas and diagnoses of GCA, TAK or who were found at surgery to have FIA were matched by age, gender and race to patients with non-inflammatory lesions including bicuspid aortic valves, chronic hypertension, Marfan syndrome and other causes of cystic medial degeneration. Total DNA, including human and bacterial, was isolated from TAA. V1-4 regions of the gene encoding bacteria-specific 16S rRNA were amplified and Sanger sequenced. Principal-coordinate analysis (PCoA) plots were created based on de novo operational taxonomic unit classification via the MacQIIME 1.7 toolkit. Hierarchical taxonomic composition of sequences was performed using a custom pipeline and visualized with Krona.

Results: Twenty-seven TAA were analyzed: 7 GCA, 5 FIA, 2 TAK, and 13 non-inflammatory. Hypertension and hyperlipidemia were the most common comorbidities, and were not significantly different between inflammatory and non-inflammatory groups.  All TAA hosted bacterial communities of varying abundance. Autoimmune-associated TAA microbiomes cluster on PCoA plots according to type of aortitis, with the clearest separation seen between FIA and TAK samples. GCA and non-inflammatory TAA microbiomes overlap on PCoA plots, but are separate from FIA and TAK. Both GCA and non-inflammatory TAA microbiomes appear to contain sub-group clusters. Gross visualization of taxonomic composition using Krona plots shows differences between GCA specimens compared to non-inflammatory samples at the phyla level, with a tendency toward increased Proteobacteria, decreased Actinobacteria, and minimal Bacteroidetes in GCA. Overall, TAA microbiomes did not show clustering by age, sex, or prednisone use. Some clustering was seen with tobacco use.

Conclusion: TAA are not sterile. Specimens from patients with different disease associations host distinct microbial communities. Further analysis is needed to assess whether differences in microbial communities play etiologic roles or are secondary results of different types of aortic injury.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/microbiomes-of-inflammatory-and-non-inflammatory-thoracic-aortic-aneurysms/