Intestine-exclusive metabolic processes involve the degradation of dietary components and xenobiotics through intricate and dynamic interactions between the host epithelial cells and gut microbiota. Disruptions in this fragile equilibrium lead to metabolic and gastrointestinal diseases, highlighting the profound impact of the gut microbiota on the host intestinal metabolic processes. Gut microbes play a crucial role in influencing intestinal metabolic homeostasis by affecting nutrient sensing, gut hormones, neurotransmitters, and redox balance, collectively modulating mucosal gene expression and metabolic signaling pathways. These intestinal-level host-microbe metabolic interactions profoundly impact extra-intestinal tissues and organs. This comprehensive review provides mechanistic insights on the crucial role of gut microbiota in sustaining metabolic health by narrowing down to the gut-level metabolic interactions.

The abundance of gut commensals has historically been associated with health-promoting effects despite the fact that the definition of good or bad microbiota remains condition-specific. The beneficial or pathogenic nature of microbiota is generally dictated by the dimensions of host-microbiota and microbe-microbe interactions. With the increasing popularity of gut microbiota in human health and disease, emerging evidence suggests opportunistic infections promoted by those gut bacteria that are generally considered beneficial. Therefore, the current review deals with the opportunistic nature of the gut commensals and aims to summarise the concepts behind the occasional commensal-to-pathogenic transformation of the gut microbes. Specifically, relevant clinical and experimental studies have been discussed on the overgrowth and bacteraemia caused by commensals. Three key processes and their underlying mechanisms have been summarised to be responsible for the opportunistic nature of commensals, viz. improved colonisation fitness that is dictated by commensal-pathogen interactions and availability of preferred nutrients; pathoadaptive mutations that can trigger the commensal-to-pathogen transformation; and evasion of host immune response as a survival and proliferation strategy of the microbes. Collectively, this review provides an updated concept summary on the underlying mechanisms of disease causative events driven by gut commensal bacteria.