Shotgun metagenomic and untargeted metabolomic analysis of gut microbiome associated with peripheral artery disease
- 1Department of Surgery, Feinberg School of Medicine, Northwestern University
Abstract
Background: While the human gut microbiome is a potentially important and modifiable risk factor for cardiovascular diseases, the links between the gut microbiome and peripheral artery disease (PAD) and its clinical subgroups (claudication and chronic limb-threatening ischemia; CLTI) are not well understood. Methods: We used shotgun metagenomics and untargeted metabolomics to analyze the fecal samples of people with PAD and age- and sex-matched non-PAD controls collected in a cross-sectional manner. We used functional prediction pathways, a network analysis, and weighted gene co-expression network analysis of metagenomic, metabolomics, and clinical data to better understand PAD-associated dysbiosis. Results: Alpha and beta diversity were similar between the PAD (n=78) and non-PAD (n=20) groups. Differentially abundant species were dominated by those belonging to the Lachnospiraceae, Ruminococcaceae and Enterobacteriaceae families. Fecal butyrate levels were reduced between the non-PAD and PAD groups, but differences were not statistically significant. There was significantly reduced alpha diversity in the samples of the CLTI compared to claudication subgroup. Abundance of multiple butyrate producers were greater in the claudication group compared to CLTI. Network analysis revealed 5 meta-modules, each with specific associations to PAD presentation and metabolomic profiles, and species that are both top module hubs and differentially abundant between groups. Community interconnectedness appears to increase in claudication, followed by community disintegration in CLTI. Conclusions: This metagenomic-metabolomic analysis of the gut microbiome of individuals with PAD, highlights the importance of studying functional capacity, diversity, and connectivity between species. Microbial modules may allow an integrative view of the microbial ecology relevant to presence and progression of PAD.
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BibTeX
@misc{niraula2026shotgun,
title = {{Shotgun metagenomic and untargeted metabolomic analysis of gut microbiome associated with peripheral artery disease}},
author = {S. Niraula and J. W. Jang and J. Jung and S. L. Stirewalt and M. E. Alagna and J. Du and C. Staley and P. Seed and S. J. Green and K. J. Ho},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.757428},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.757428v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Shotgun metagenomic and untargeted metabolomic analysis of gut microbiome associated with peripheral artery disease
AU - S. Niraula
AU - J. W. Jang
AU - J. Jung
AU - S. L. Stirewalt
AU - M. E. Alagna
AU - J. Du
AU - C. Staley
AU - P. Seed
AU - S. J. Green
AU - K. J. Ho
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.757428
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.757428v1
AB - Background: While the human gut microbiome is a potentially important and modifiable risk factor for cardiovascular diseases, the links between the gut microbiome and peripheral artery disease (PAD) and its clinical subgroups (claudication and chronic limb-threatening ischemia; CLTI) are not well understood. Methods: We used shotgun metagenomics and untargeted metabolomics to analyze the fecal samples of people with PAD and age- and sex-matched non-PAD controls collected in a cross-sectional manner. We used functional prediction pathways, a network analysis, and weighted gene co-expression network analysis of metagenomic, metabolomics, and clinical data to better understand PAD-associated dysbiosis. Results: Alpha and beta diversity were similar between the PAD (n=78) and non-PAD (n=20) groups. Differentially abundant species were dominated by those belonging to the Lachnospiraceae, Ruminococcaceae and Enterobacteriaceae families. Fecal butyrate levels were reduced between the non-PAD and PAD groups, but differences were not statistically significant. There was significantly reduced alpha diversity in the samples of the CLTI compared to claudication subgroup. Abundance of multiple butyrate producers were greater in the claudication group compared to CLTI. Network analysis revealed 5 meta-modules, each with specific associations to PAD presentation and metabolomic profiles, and species that are both top module hubs and differentially abundant between groups. Community interconnectedness appears to increase in claudication, followed by community disintegration in CLTI. Conclusions: This metagenomic-metabolomic analysis of the gut microbiome of individuals with PAD, highlights the importance of studying functional capacity, diversity, and connectivity between species. Microbial modules may allow an integrative view of the microbial ecology relevant to presence and progression of PAD.
ER -