Autophagy as a Proposed Regulatory Interface in the Gut Microbiota-Cardiovascular Axis.
- 1Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.
- 2Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
Abstract
The gut-cardiovascular axis is increasingly recognized as a contributor to cardiovascular disease (CVD) risk; however, most available evidence remains associative, and the mechanistic links between gut dysbiosis, autophagy, and cardiovascular pathology require further validation. This review proposes a conceptual framework in which autophagy may serve as a regulatory interface linking gut microbiota-derived signals with vascular and cardiac dysfunction. We summarize evidence that microbial metabolites, including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and dysbiosis-associated products such as lipopolysaccharide (LPS), may influence autophagic flux in intestinal epithelial cells, endothelial cells, macrophages, and myocardium through pathways involving TLR-MyD88-NF-κB/NLRP3 signaling, AMPK-mTOR-ULK1-Beclin-1 regulation, and FXR/TGR5-associated mechanisms. These pathways may contribute to oxidative stress, lipid dysregulation, gut barrier dysfunction, endothelial activation, foam cell formation, and cardiovascular inflammation. We also discuss selected inflammatory and metabolic biomarkers, including PCSK9, MPO, Lp-PLA2, TMAO, and CRP, while emphasizing that their relationships with autophagy are context-dependent and, in several cases, indirect. Emerging therapeutic opportunities, including microbiome remodeling, prebiotics, probiotics, postbiotic SCFAs, high-purity eicosapentaenoic acid, PCSK9 inhibition, and autophagy-targeted nanocarriers, are evaluated with attention to their current evidence level. As many of these approaches remain supported mainly by preclinical, mechanistic, or indirect clinical evidence, future translation will require longitudinal human studies, standardized autophagy-flux assessment, multi-omics integration, and well-designed clinical trials using clinically relevant cardiovascular endpoints. Overall, this review positions the gut microbiota-autophagy-cardiovascular axis as a testable conceptual model to guide future mechanistic and translational research in CVD.
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BibTeX
@article{ramirez2026autophagy,
title = {{Autophagy as a Proposed Regulatory Interface in the Gut Microbiota-Cardiovascular Axis.}},
author = {Salam Almoghrabi Ramirez and Mai Mohamed Karousa and Esraa Yassin and Anas AlOrjan and Salima Shebbo and Amal Al-Haidose and Asad Zeidan and Atiyeh M Abdallah},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s590787},
url = {https://europepmc.org/article/MED/42903294},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Autophagy as a Proposed Regulatory Interface in the Gut Microbiota-Cardiovascular Axis.
AU - Salam Almoghrabi Ramirez
AU - Mai Mohamed Karousa
AU - Esraa Yassin
AU - Anas AlOrjan
AU - Salima Shebbo
AU - Amal Al-Haidose
AU - Asad Zeidan
AU - Atiyeh M Abdallah
PY - 2026
DA - 2026/10/13
JO - Journal of inflammation research
DO - 10.2147/jir.s590787
UR - https://europepmc.org/article/MED/42903294
AB - The gut-cardiovascular axis is increasingly recognized as a contributor to cardiovascular disease (CVD) risk; however, most available evidence remains associative, and the mechanistic links between gut dysbiosis, autophagy, and cardiovascular pathology require further validation. This review proposes a conceptual framework in which autophagy may serve as a regulatory interface linking gut microbiota-derived signals with vascular and cardiac dysfunction. We summarize evidence that microbial metabolites, including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and dysbiosis-associated products such as lipopolysaccharide (LPS), may influence autophagic flux in intestinal epithelial cells, endothelial cells, macrophages, and myocardium through pathways involving TLR-MyD88-NF-κB/NLRP3 signaling, AMPK-mTOR-ULK1-Beclin-1 regulation, and FXR/TGR5-associated mechanisms. These pathways may contribute to oxidative stress, lipid dysregulation, gut barrier dysfunction, endothelial activation, foam cell formation, and cardiovascular inflammation. We also discuss selected inflammatory and metabolic biomarkers, including PCSK9, MPO, Lp-PLA2, TMAO, and CRP, while emphasizing that their relationships with autophagy are context-dependent and, in several cases, indirect. Emerging therapeutic opportunities, including microbiome remodeling, prebiotics, probiotics, postbiotic SCFAs, high-purity eicosapentaenoic acid, PCSK9 inhibition, and autophagy-targeted nanocarriers, are evaluated with attention to their current evidence level. As many of these approaches remain supported mainly by preclinical, mechanistic, or indirect clinical evidence, future translation will require longitudinal human studies, standardized autophagy-flux assessment, multi-omics integration, and well-designed clinical trials using clinically relevant cardiovascular endpoints. Overall, this review positions the gut microbiota-autophagy-cardiovascular axis as a testable conceptual model to guide future mechanistic and translational research in CVD.
SN - 1178-7031
ER -