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The role of the gut microbiome in human health and disease is being increasingly recognized. Gut microbes (including bacteria, fungi and viruses) can be genetically modified to diagnose (as biosensors) and treat (detoxification, controlled biosynthesis and precision targeting) the dysbiosis of the microbiome, which has been linked to several cancers and metabolic, autoimmune and infectious diseases. However, conventional manipulation of single microbial strains is often insufficient, and engineering a mutually supportive and collaborative network of gut microbes — ‘a keystone consortium’ — could be more effective. In this Review, we summarize gut microbiome engineering strategies against selected diseases and critically discuss their translational potential. We focus mainly on genetic engineering approaches, but we also discuss complementary strategies such as encapsulation, coupling with electronic …