Gut Microbiota as a Modulator of Age-related Arterial Thrombosis

Introduction Aging is a natural process accompanied by a heightened susceptibility to thrombotic diseases [ 1 ] [ 2 ]. Alongside classical hallmarks such as dysfunctional vascular phenotypes and increased levels of coagulation factors, older individuals undergo profound changes in their gut microbial composition [ 3 ]. Disturbances of the gut microbiome have been implicated with impaired gut barrier function and chronic inflammation, both factors driving cardiovascular pathologies [ 4 ]. Given these interconnected processes, we aim to identify age-related microbial shifts that may promote prothrombotic states in the elderly host. Method C57BL/6J and low-density lipoprotein receptor-deficient mice ( Ldlr -/- ) were maintained under either germ-free (GF) or conventionally raised (CONV-R) housing conditions. Animals were examined in two age groups: (1) young mice (17-23 weeks old); (2) aged mice (65-74 weeks old). To assess the arterial thrombosis risk, von Willebrand factor (VWF) ELISA and the carotid artery ligation model were employed. In this in vivo thrombosis model, adhesion of rhodamine B-stained platelets to the injured vessel wall was visualized in real‑time by epifluorescence high-speed intravital microscopy. Additionally, 16S bacterial ribosomal RNA gene sequencing targeting the hypervariable V3-V4 region (Illumina MiSeq) was performed on cecal stool samples to characterize changes in gut microbial composition. Furthermore, inflammatory protein signatures were quantified using a proximity extension assay (Olink). Results In aged C57BL/6J mice, we observed elevated VWF levels and enhanced platelet deposition to the site of injury in the carotid artery ligation model. To characterize microbial taxa that are influenced by aging, 16S ribosomal RNA gene sequencing was performed. Aging markedly altered the gut microbiome profile, notably shown by a loss of protective bacterial genera such as the commensal Bacteroides spp . In addition, depletion of taxa with anti-inflammatory properties including Lactobacillus and Faecalibaculum , may reflect a reduced production of short-chain fatty acids and anti-inflammatory peptides, respectively. Similarly, aged hypercholesteremic Ldlr -/- mice displayed an altered gut microbial profile accompanied by increased VWF levels. Further, O-Link proteomic analysis revealed elevated levels of pro-inflammatory mediators such as IL-17 and IL23R in aged mice. Interestingly, this phenotype was completely abolished in both young and aged germ-free animals, highlighting a critical role of gut microbes in mediating systemic inflammation in aging. Conclusion Here, we report that aging acts as a crucial modifier of arterial thrombosis. Age-related alterations in gut microbial composition promote a pro-inflammatory phenotype, highlighting the gut microbiota as a modifiable, age-dependent cardiovascular risk factor. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany