Dietary (poly)phenols mitigate inflammatory bowel disease: Therapeutic targets, mechanisms of action, and clinical observations

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are a rapidly growing public health concern worldwide. These diseases are heterogeneous at the clinical, immunological, molecular, genetic, and microbial level, but characteristically involve a disrupted immune-microbiome axis. Shortcomings in conventional treatment options warrant the need for novel therapeutic strategies to mitigate these life-long and relapsing disorders of the gastrointestinal tract. Polyphenols, a diverse group of phytochemicals, have gained attention as candidate treatments due to their array of biological effects. Polyphenols exert broad anti-inflammatory and antioxidant effects through the modulation of cellular signaling pathways and transcription factors important in IBD progression. Polyphenols also bidirectionally modulate the gut microbiome, supporting commensals and inhibiting pathogens. One of the primary means by which gut microbiota interface with the host is through the production of metabolites, which are small molecules produced as intermediate or end products of metabolism. There is growing evidence to support that modulation of the gut microbiome by polyphenols restores microbially derived metabolites critical to the maintenance of intestinal homeostasis that are adversely disrupted in IBD. This review aims to define the therapeutic targets of polyphenols that may be important for mitigation of IBD symptoms, as well as to collate evidence for their clinical use from randomized clinical trials.