The incidence of type 1 diabetes (T1D), an autoimmune disease commonly diagnosed in childhood, has been steadily increasing since World War II. Lifestyle factors such as infant diet, antibiotics, enteric viral infections, increasing Caesarean births and unhealthy foods have all been implicated in disease risk. Gut bacteria (the ‘microbiome’) are likely mediators of many of these factors. Using multiomics on stool and other samples from cohorts of children before T1D onset, including metagenomics, proteomics, metabolomics and viromics we demonstrate how microbes and viruses are contributing to disrupting the gut epithelium and altering host metabolism during development of autoimmunity. In a world-first clinical trial we have used a microbiome-targeted dietary supplement in adults with T1D to remodel the gut bacterial composition and function. We show that faecal transplantation of the human microbiome after the diet can transfer diabetes protection into germ-free mice. Diabetes protection was linked to the microbial function assessed by metabolomics rather than the composition of the microbiota. This demonstrates the potential of targeting the gut microbiota in T1D and using multiomics to understand the complexities of the system.