Abstract
Objective:We sought to characterize microbiomes of thoracic aortas from patients with non-infectious aortitis due to giant cell arteritis (GCA) and clinically isolated aortitis (CIA) and to compare them to non-inflammatory aorta aneurysm controls. We also compared microbiomes from concurrently processed and separately reported temporal arteries (TA) and aortas.Methods:From 220 prospectively enrolled patients undergoing surgery for thoracic aorta aneurysm, 49 were selected. Inflammatory and non-inflammatory cases were selected based on ability to match for age (+/-10 years), gender, and race. Biopsies were collected under aseptic conditions and snap-frozen. Taxonomic classification of bacterial sequences was performed to the genus level and relative abundances were calculated. Microbiome differential abundances were analyzed by principal coordinates analysis.Results:Forty-nine patients with thoracic aortic aneurysms (12 CIA, 14 GCA, 23 non-inflammatory aneurysms) were enrolled. Alpha (P=0.018) and beta (P=0.024) diversity differed between specimens from aortitis cases and controls. There were no significant differences between CIA and GCA (P>0.7). The largest differential abundances between non-infectious aortitis and non-inflammatory control samples included Enterobacteriaceae, Phascolarctobacterium, Acinetobactor, Klebsiella, and Prevotella. Functional metagenomic predictions with PICRUSt revealed enrichment of oxidative phosphorylation and porphyrin metabolism pathways and downregulation of transcription factor pathways in aortitis compared to controls. Microbiomes of aortic samples differed significantly from temporal artery samples from a companion study, in both control and GCA groups (P=0.0002).Conclusion:Thoracic aorta aneurysms, far from being sterile, contain unique microbiomes that differ from those found in temporal arteries. The aorta microbiomes are most similar between aneurysms that were associated with inflammation, GCA, and CIA, but differed from those associated with non-inflammatory etiologies. These findings are promising in that they indicate that microbes may play a role in the pathogenesis of aortitis-associated aneurysms or non-inflammatory aneurysms by promoting or protecting against inflammation. However, we cannot rule out that these changes are related to alterations in tissue substrate that favor secondary changes in microbial communities.
Highlights
This latter group has been the focus of recent consensus guidelines and coining the term “clinically isolated aortitis” (CIA) to indicate a focal-regional non-infectious form of vasculitis usually restricted to the proximal thoracic aorta [3, 4]
Among numerous questions raised by such studies are the following: First, is CIA a limited presentation of diseases within a spectrum of large vessel vasculitis (LVV), including giant cell arteritis (GCA)? Second, do common conditions exist within CIA-affected and GCA-affected aortas and GCA-affected temporal arteries that favor developing inflammatory aneurysms or temporal artery inflammation and stenoses? And third, if this were the case, would those conditions differ from that present in non-inflammatory thoracic aortic aneurysms? Because of our interests in infectious triggers and vascular properties that favor the genesis of vasculitis, we examined the vascular microbiome in subsets of aortitis and non-inflammatory aorta aneurysm controls [8,9,10,11]
There were no differences in demographics, exposures, and relevant past history among the 3 groups, except for tobacco use (P=0.02), a history of coronary artery disease (P=0.05), and steroid use in 4/14 patients with GCA (Table 1)
Summary
Aortitis may appear in isolation, as a topographically limited lesion This latter group has been the focus of recent consensus guidelines and coining the term “clinically isolated aortitis” (CIA) to indicate a focal-regional non-infectious form of vasculitis usually restricted to the proximal thoracic aorta [3, 4]. In a recent study of 196 patients with non-infectious aortitis, 66% had diagnoses of CIA, 21% had GCA, 7% had TAK, and 6% had other systemic inflammatory diseases, at the time of surgery. Because of our interests in infectious triggers and vascular properties that favor the genesis of vasculitis, we examined the vascular microbiome in subsets of aortitis and non-inflammatory aorta aneurysm controls [8,9,10,11]. Unlike prior microbiome studies of large vessels, we collected surgically aseptic specimens that were snap-frozen and not fixed in formalin or paraffin-embedded
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