Gut Microbiota, Oxidative Stress, and Extracellular Vesicles: Molecular Crosstalk in Inflammation and Disease and Therapeutic Interventions

Hassan Ali^1,2,3, Tsvetelina Velikova^3,*, Petya Marinova³
1 Institute of Microbiology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad, Pakistan
2 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
3 Medical Faculty, Sofia University St. Kliment Ohridski, 1 Kozyak str, Sofia, Bulgaria
* Corresponding Author: Tsvetelina Velikova. Email: email , email
(This article belongs to the Special Issue: Cellular and Molecular Mechanisms of Gut Microbiota, Oxidative Stress, and Inflammation in Health and Disease)

BIOCELL https://doi.org/10.32604/biocell.2026.081372

Received 28 February 2026; Accepted 05 June 2026; Published online 03 July 2026

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Abstract

The gut microbiota, oxidative stress, and extracellular vesicles (EVs) form an interdependent triad essential for gastrointestinal homeostasis and systemic health. This narrative review summarizes the molecular crosstalk among these components in inflammation and disease. Literature was retrieved from PubMed and Scopus using relevant keywords and reference screening. Gut microbes regulate redox balance through metabolites such as short-chain fatty acids and modulation of host reactive oxygen species (ROS) production via mitochondrial pathways and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Dysbiosis has been associated with excessive ROS generation, impaired antioxidant defenses, and activation of redox-sensitive signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK), contributing to inflammatory and metabolic diseases. EVs act as mediators of host-microbe communication by transferring bioactive cargo that may influence oxidative stress, immune responses, and epithelial integrity. Host-derived EVs, shaped by redox status, may further contribute to systemic inflammation associated with chronic diseases. Therapeutic strategies include microbiota modulation, antioxidants, nuclear factor erythroid 2-related factor 2 (Nrf2) activators, NADPH oxidase inhibitors, and EV-based interventions. Integrated multi-omics and standardized EV profiling are needed for precision medicine approaches.