Dietary Bioactive Compounds: Cellular Sensory Pathways, Microbial Partners, and Clinical Realities

Background/Objectives: Dietary bioactive compounds (BCs) modulate multiple cellular pathways involved in inflammation, oxidative stress, energy metabolism, and tissue homeostasis. This narrative review aimed to synthesize the mechanistic roles and therapeutic relevance of major dietary BC classes, including polyphenols, carotenoids, organosulfur compounds, and polyunsaturated fatty acids, in chronic non-communicable diseases. Methods: We conducted a narrative review to integrate current evidence on the classification, bioavailability, molecular targets, microbiota interactions, and clinical relevance of dietary BCs. The literature considered experimental, observational, and clinical studies addressing key signaling pathways, including NF-κB, Nrf2, AMPK, mTOR, SIRT1, PPARs, and the NLRP3 inflammasome, as well as the diet-microbiota-host axis. Results: The literature indicates that BCs exert pleiotropic effects through the coordinated modulation of transcription factors, metabolic sensors, nuclear receptors, and inflammatory mediators. Their biological activity is also shaped by bioavailability, food matrix effects, host metabolism, and gut microbial transformation into bioactive metabolites. Across obesity, type 2 diabetes, cardiovascular disease, inflammatory bowel disease, and neurodegenerative conditions, BCs appear associated with improved inflammatory, metabolic, and redox regulation. However, findings remain limited by heterogeneity in study design, intervention duration, and compound characterization. Conclusions: Dietary BCs show therapeutic potential as modulators of molecular and microbial pathways relevant to chronic diseases. However, greater standardization in study design and longer-term human trials are needed to support robust evidence-based recommendations.