The recognition that intestinal microbiota exert profound effects on human health has led to major advances in our understanding of disease processes. Studies over the past 20 years have shown that host components, including components of the host immune system, shape the microbial community. Pathogenic alterations in commensal microorganisms contribute to disease manifestations that are generally considered to be noncommunicable, such as inflammatory bowel disease, diabetes mellitus and liver disease, through a variety of mechanisms, including effects on host immunity. More recent studies have shed new light on how the immune system and microbiota might also drive the pathogenesis of renal disorders. In this Review, we discuss the latest insights into the mechanisms regulating the microbiome composition, with a focus both on genetics and environmental factors, and describe how commensal microorganisms calibrate innate and adaptive immune responses to affect the activation threshold for pathogenic stimulations. We discuss the mechanisms that lead to intestinal epithelial barrier inflammation and the relevance of certain bacteria to the pathogenesis of two common kidney-based disorders: hypertension and renal stone disease. Limitations of current approaches to microbiota research are also highlighted, emphasizing the need to move beyond studies of correlation to causation.