Perivascular adipose tissue transcriptome reveals microbe-, immune- and inflammation-enriched remodeling in a murine IBD model

Inflammatory Bowel Disease (IBD) is characterized by chronic intra- and extra-intestinal inflammation, including vascular dysfunction and cardiovascular disease risk. Emerging evidence suggests that perivascular adipose tissue (PVAT), an immunometabolic organ surrounding blood vessels, becomes pro-contractile in IBD and may act as a conduit linking gut inflammation to vascular dysfunction. This study uses genomic sequencing to test the hypotheses that PVAT in IBD (1) contains an altered microbial profile, (2) expresses genes associated with inflammation, and (3) causes a pro-inflammatory genome shift in isolated macrophages. Experiments use an IL-10-/- + H. hepaticus (IBD) mouse model of IBD, with non-gavaged (IL10NG) and IL-10+/+ (WT) control mice. To explore microbiome–vascular crosstalk, Study #1 analyzed bacterial communities of mesenteric mPVAT, aortic aPVAT, visceral fat, and cecal contents using 16S rRNA sequencing. In Study #2, bulk RNA-sequencing of mPVAT identified differentially expressed genes (DEGs) and enriched pathways underlying vascular dysfunction. Study #3 utilized bulk RNA-sequencing of RAW 264.7 macrophages treated with WT, IL10N, or IBD PVAT-conditioned media to define macrophage responses to the PVAT secretome. In Study #1, IBD markedly alters microbial populations of cecal contents as well as PVAT and non-PVAT adipose. Beta-diversity analyses showed clear separation between WT, ILG, and ILNG mice, indicating shifts in microbial composition and lineage structure. IBD PVAT displayed increased abundance of inflammation-associated taxa, including Proteobacteria, Fusobacteriota, and Campylobacterota, suggesting dysbiosis extends beyond the gut. In Study #2, mPVAT demonstrated extensive transcriptional reprogramming in IBD mice. DEGs highlighted upregulation of oxidative phosphorylation, electron transport chain, cytokine signaling, and extracellular matrix remodeling pathways, consistent with metabolically activated and inflamed PVAT. Immune-related pathways such as IL-1β production, chemokine signaling, and neutrophil extracellular trap formation were significantly enriched, indicating heightened immune activation within IBD PVAT. Study #3 assessing the mPVAT effect on RAW 264.7 macrophages found that, consistent with Study #2 results, IBD PVAT–conditioned media induced expression of inflammatory genes and markers in macrophages. The upregulated genes are associated with enhanced prostaglandin synthesis, immune cell recruitment, and disrupted cytokine regulation, driving a macrophage phenotype favoring inflammation, tissue damage, and impaired resolution. These studies collectively reveal that IBD promotes microbial infiltration and immune–metabolic reprogramming that extend beyond the gut into PVAT. These alterations underscore a mechanistic link between intestinal inflammation and vascular dysfunction that involves PVAT signaling as a mediator. The data provide insight that will guide future mechanistic studies aimed at presenting or resolving PVAT and vascular dysfunction in IBD. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.