In inflammatory bowel disease and extraintestinal manifestations: What role does microbiome play?

•This review aims at conveying the roles of microbiome in inflammatory bowel disease and extraintestinal manifestations.•A critical analysis of current development and challenges is presented.•A comprehensive perception into therapies of inflammatory bowel disease and extraintestinal manifestations with the assistance of microbiota is presented.•The advantages and common systems of adapted microbial engineering on improving therapeutic efficiency are discussed.•A perspective on their future development is presented. Inflammatory bowel disease (IBD) is a systemic disorder affecting intestinal tract and other organs outside the gut, known as extraintestinal manifestations (EIMs). These EIMs are complex and diverse, and early treatment may reduce teratogenic rates and improve quality of life. However, our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight. Fortunately, advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs. The gut microbiota can drive aberrant immune activation and intestinal inflammation. Intriguingly, chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis. Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function. Furthermore, gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites, leading to systemic inflammatory responses. The microbiome is showing its potential in treating IBD and EIMs, and microbial engineering approaches, such as probiotic engineering and engineered fecal microbiota transplantation, are exhibiting great promise for IBD therapeutics.