Microbiota-Gut-Brain Axis Disruption, Neuroinflammation, and Potential Antioxidant-Based Treatments in Metabolic Diseases.

Metabolic diseases are strongly associated with chronic systemic inflammation and oxidative stress, which disrupt the microbiota-gut-brain (MGB) axis and promote neuroinflammation. Dysbiosis favors the release of proinflammatory metabolites, reactive oxygen species (ROS), and lipopolysaccharides (LPS), increasing intestinal permeability and triggering systemic immune responses that reach the central nervous system (CNS) through a weakened blood-brain barrier (BBB). This review summarizes current knowledge on the pathophysiological mechanisms linking the MGB axis, metabolic disorders, and neuroinflammation, as well as the therapeutic potential of antioxidants. A literature search was conducted in PubMed, Web of Science, Scopus, and ScienceDirect and included original research articles, reviews, clinical trials, and meta-analyses related to microbiota, neuroinflammation, oxidative stress, and antioxidant interventions. Evidence indicates that dysbiosis exacerbates metabolic dysfunction by activating the nuclear factor kappa B (NF-κB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, while excessive ROS production impairs mitochondrial function, neuronal survival, and cognitive processes. Antioxidant strategies, including polyphenols, omega-3 fatty acids, curcumin, vitamins C and E, and probiotics, can restore microbial diversity, reinforce intestinal and BBB integrity, and modulate oxidative and inflammatory signaling. In conclusion, supplements and bacteria with antioxidant properties show promising therapeutic effects by targeting oxidative stress mechanisms involved in metabolic diseases and their pathological consequences, such as dysbiosis and neuroinflammation.