Muhammad Tayyab Arshad, Sammra Maqsood, Ali Ikram, Baojun Xu
Chronic diseases such as diabetes, cancer, cardiovascular disease, and neurological disorders are among the major causes of the global health burden. Functional food intake is one of the most vital lifestyle variables for preventing such diseases. Blueberries ( Vaccinium spp .) are a functional food rich in polyunsaturated fatty acids and bioactive compounds such as phenolic acids, flavonoids, carotenoids, and anthocyanins. They are powerful anti-inflammatory, antioxidant, and metabolic-regulating compounds. This review addresses the molecular mechanisms involved in the protective effects of blueberry bioactive compounds and their influence on oxidative stress, inflammation, metabolic pathways, blood pressure regulation pathways, lipid-lowering pathways, vascular health, anticancer, antidiabetic, neuroprotective, anti-obesity, and gut microbiota composition. Blueberry bioactives stimulate healthy bacteria to increase by modifying the gut microbiota. The short-chain fatty acids (SCFAs) produced by these healthy bacteria suppress NF-κB and enhance anti-inflammatory signaling which decreases inflammation in the intestines. It discusses the challenges and ways to overcome the bioavailability issues of these compounds and provides clinical evidence that demonstrates the efficacy of blueberries in preventing chronic diseases. Finally, we emphasize the importance of tailoring dietary interventions, bioavailability, and the challenges of achieving maximal benefits from blueberries and a potential synergistic effect when used with other bioactive-rich foods. The incorporation of blueberries into public health measures may be a way to personalize therapy and control chronic diseases.