Chronic kidney disease (CKD) is associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality that cannot be fully explained by traditional risk factors. Emerging evidence highlights the central role of the gut–kidney–heart axis, whereby gut microbiota dysbiosis promotes the generation and systemic accumulation of uremic toxins, including indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO). These metabolites contribute to endothelial dysfunction, oxidative stress, inflammation, and vascular remodeling, thereby accelerating CV disease progression in CKD. Dietary patterns represent a key modifiable factor influencing gut microbiota composition and metabolic activity. The Mediterranean diet, characterized by high intake of plant-based foods, dietary fiber, and polyphenols, and low consumption of red and processed meats, has emerged as a promising microbiota-targeted strategy. It promotes saccharolytic fermentation, enhances short-chain fatty acid production, and reduces proteolytic pathways responsible for uremic toxin generation. Accumulating evidence from observational studies, meta-analyses, and dietary intervention trials suggests that adherence to Mediterranean and plant-based dietary patterns is associated with reduced uremic toxin burden, improved renal outcomes, and lower CV risk in CKD populations. However, direct interventional evidence linking Mediterranean diet adherence to changes in specific uremic toxin levels remains limited. This narrative review summarizes current evidence on diet–microbiota interactions in CKD and highlights the Mediterranean diet as a biologically plausible strategy for targeting the gut–kidney–heart axis. Future well-designed randomized controlled trials (RCTs) are needed to confirm causal relationships and support clinical implementation.

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes.