The Restorative Role of Flavonoids in Immunological, Antioxidant, and Microbiota Mechanisms of Autoimmune Thyroiditis

Autoimmune thyroiditis is a multifactorial endocrine disorder characterized by chronic immune-mediated inflammation, oxidative imbalance, and disruption of gut microbiota homeostasis. These pathological processes lead to thyroid hormone deficiency, metabolic dysfunction, and systemic immune polarization. The present study aimed to evaluate the immunological, antioxidant, and microbiota-corrective effects of three plant-derived flavonoids - quercetin, dihydroquercetin (taxifolin), and luteolin - in an experimental rat model of autoimmune thyroiditis. Thyroid hormone concentrations (T3, T4, and fT3), antioxidant enzyme activity (GPX1), macro- and microelement balance (Ca²⁺, Mg²⁺, Fe, K⁺ and P), and intestinal bacterial composition were analyzed to assess the extent of restoration. Autoimmune thyroiditis caused a pronounced decrease in thyroid hormone levels (T3 −66.5%, T4 −66.7% and fT3 −39.5%) and GPX1 activity (−59.1%), along with disturbances in essential macro- and microelements and microbiota composition. Flavonoid treatment markedly ameliorated these impairments: luteolin restored T3 and T4 levels to near-physiological values and normalized GPX1 activity by 93.6% of the control. Quercetin and dihydroquercetin showed moderate but significant improvements in antioxidant and endocrine parameters. Additionally, flavonoid supplementation rebalanced the gut microbiota, increasing beneficial taxa (Lactobacillus, Bifidobacterium and Faecalibacterium prausnitzii) while reducing pathogenic species (Escherichia coli, Streptococcus and Fusobacterium). Collectively, the findings demonstrate that natural flavonoids exert a potent corrective influence on immune, redox, and microbiota disturbances in autoimmune thyroiditis. Among them, luteolin exhibited the strongest integrative effect, suggesting its potential as a promising adjunctive therapy to conventional treatment in thyroid autoimmune diseases. HIGHLIGHTS Autoimmune thyroiditis induced severe endocrine, oxidative, and microbiota disturbances in rats. Dietary flavonoids significantly restored thyroid hormone homeostasis and antioxidant defense. Luteolin exhibited the strongest integrative effects on GPX1 activity and immune modulation. Flavonoid treatment rebalanced gut microbiota by increasing beneficial and reducing pathogenic taxa. Natural flavonoids represent promising functional agents for correcting immune-redox-microbiota dysregulation in AIT. GRAPHICAL ABSTRACT

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