Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives
Xiaopeng Li, Enjun Xie, Shumin Sun, Jie Shen, Yujin Ding, Jiaqi Wang, Xiaoyu Peng, Ruting Zheng, Mohamed A. Farag, Jianbo Xiao
Abstract
• Elucidates the metabolism of flavonoids within the human body involving the intestine, gut microbiota, and liver. • The multifaced functions of flavonoids in the gastrointestinal tract are provided, including regulating nutrients metabolism, gut hormone secretion, and reshaping gut microbiota. • The associated systemic effects of flavonoids on metabolic homeostasis in peripheral organs are summarized. • Dietary flavonoids benefit several disease progressions, and the safety and future prospects are also illustrated. Flavonoids are naturally occurring dietary phytochemicals with significant antioxidant effects aside from several health benefits. People often consume them in combination with other food components. Compiling data establishes a link between bioactive flavonoids and prevention of several diseases in animal models, including cardiovascular diseases, diabetes, gut dysbiosis, and metabolic dysfunction-associated steatotic liver disease (MASLD). However, numerous clinical studies have demonstrated the ineffectiveness of flavonoids contradicting rodent models, thereby challenging the validity of using flavonoids as dietary supplements. This review provides a clinical perspective to emphasize the effective roles of dietary flavonoids as well as to summarize their specific mechanisms in animals briefly. First, this review offers an in-depth elucidation of the metabolic processes of flavonoids within human, encompassing the small, large intestine, and the liver. Furthermore, the review provides a comprehensive overview of the various functions of flavonoids in the gastrointestinal tract, including hindering the breakdown and assimilation of macronutrients, such as polysaccharides and lipids, regulating gut hormone secretion as well as inhibition of mineral iron absorption. In the large intestine, an unabsorbed major portion of flavonoids interact with the gut flora leading to their biotransformation. Once absorbed and circulated in the bloodstream, bioactive flavonoids or their metabolites exert numerous beneficial systemic effects. Lastly, we examine the protective effects of flavonoids in several metabolic disorders, including endothelial dysfunction, MASLD, cardiovascular disease, obesity, hyperlipidemia, and insulin resistance. In conclusion, this review outlines the safety and future prospects of flavonoids in the field of health, especially in the prevention of metabolic syndrome (MetS).