Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives
- 1Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia
- 2Laboratory for Cardiometabolic Research, University of Split School of Medicine, 21000 Split, Croatia
- 3Department of Maxillofacial Surgery, University Hospital of Split, 21000 Split, Croatia
Abstract
Cardiometabolic diseases are increasingly recognized as disorders of chronic low-grade systemic inflammation and gut barrier dysfunction that mutually reinforce one another. Each condition amplifies the other through progressive injury to the intestinal epithelium. Compromise of the mucus layer, altered tight junction dynamics, dysbiosis, and impaired epithelial restitution promote intestinal permeability and enable the translocation of lipopolysaccharide and other microbial products into the circulation, thereby inducing metabolic endotoxemia. This gut derived inflammatory signal activates Toll like receptor 4, nuclear factor kappa B, and inflammasome associated pathways, linking barrier dysfunction to insulin resistance, hepatic steatosis, adipose tissue inflammation, endothelial activation, and vascular injury. Here, we examine the gut barrier as an immunometabolic interface and synthesize current evidence connecting its disruption to endotoxin driven cardiometabolic pathology. We further evaluate selected natural bioactive compounds, including curcumin, resveratrol, quercetin, epigallocatechin gallate, berberine, anthocyanins, omega 3 polyunsaturated fatty acids, and dietary polysaccharides, as gut targeted interventions capable of reinforcing junctional integrity, restoring mucus and microbial homeostasis, lowering endotoxin burden, and attenuating inflammatory signaling. Finally, we highlight the principal translational barriers that currently limit clinical implementation, including pharmacokinetic variability, microbiota dependent biotransformation, source standardization, and the lack of robust, standardized biomarkers of barrier restoration and metabolic endotoxemia.
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BibTeX
@article{santic2026natural,
title = {{Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives}},
author = {Roko Šantić and Lovre Martinovic and Nikola Pavlović and Dinko Martinović and Josip Vrdoljak and Marko Kumrić and Marino Vilović and Joško Božić},
journal = {Molecules},
year = {2026},
month = may,
doi = {10.3390/molecules31111840},
url = {https://doi.org/10.3390/molecules31111840},
note = {CC BY},
}
RIS
TY - JOUR
TI - Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives
AU - Roko Šantić
AU - Lovre Martinovic
AU - Nikola Pavlović
AU - Dinko Martinović
AU - Josip Vrdoljak
AU - Marko Kumrić
AU - Marino Vilović
AU - Joško Božić
PY - 2026
DA - 2026/05/27
JO - Molecules
DO - 10.3390/molecules31111840
UR - https://doi.org/10.3390/molecules31111840
AB - Cardiometabolic diseases are increasingly recognized as disorders of chronic low-grade systemic inflammation and gut barrier dysfunction that mutually reinforce one another. Each condition amplifies the other through progressive injury to the intestinal epithelium. Compromise of the mucus layer, altered tight junction dynamics, dysbiosis, and impaired epithelial restitution promote intestinal permeability and enable the translocation of lipopolysaccharide and other microbial products into the circulation, thereby inducing metabolic endotoxemia. This gut derived inflammatory signal activates Toll like receptor 4, nuclear factor kappa B, and inflammasome associated pathways, linking barrier dysfunction to insulin resistance, hepatic steatosis, adipose tissue inflammation, endothelial activation, and vascular injury. Here, we examine the gut barrier as an immunometabolic interface and synthesize current evidence connecting its disruption to endotoxin driven cardiometabolic pathology. We further evaluate selected natural bioactive compounds, including curcumin, resveratrol, quercetin, epigallocatechin gallate, berberine, anthocyanins, omega 3 polyunsaturated fatty acids, and dietary polysaccharides, as gut targeted interventions capable of reinforcing junctional integrity, restoring mucus and microbial homeostasis, lowering endotoxin burden, and attenuating inflammatory signaling. Finally, we highlight the principal translational barriers that currently limit clinical implementation, including pharmacokinetic variability, microbiota dependent biotransformation, source standardization, and the lack of robust, standardized biomarkers of barrier restoration and metabolic endotoxemia.
SN - 1420-3049
SN - 1433-1373
ER -