The gastrointestinal tract encounters a wide variety of microorganisms, including beneficial symbionts, pathobionts, and pathogens. Recent evidence has shown that the gut microbiota, directly or indirectly through its components, such as metabolites, actively participates in the host inflammatory response by cytokine-microbiota or microbiota-cytokine modulation interactions, both in the gut and systemically. Therefore, further elucidation of host cytokine molecular pathways and microbiota components will provide a novel and promising therapeutic approach to control or prevent inflammatory disease and to maintain host homeostasis. The purpose of this review is to summarize well-established scientific findings and provide an updated overview regarding the direct and indirect mechanisms by which the gut microbiota can influence the inflammatory response by modulating the host's cytokine pathways that are mostly involved, but not exclusively so, with gut homeostasis. In addition, we will highlight recent results from our group, which suggest that the microbiota promotes cytokine release from inflammatory cells though activation of microbial metabolite sensor receptors that are more highly expressed on inflammatory and intestinal epithelial cells.