The gastrointestinal ecosystem is a highly complex environment that can have a profound influence on human health. Inflammation in the gut, linked to increased intestinal permeability and an altered gut microbiome has been linked to the development of multiple human diseases including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract are also thought to play a role in T1D pathogenesis possibly via similar mechanisms. Yet the inter-relationship between the gut virome, microbiome and host-function have not been studied. Here, we have applied an integrative approach to combine fecal virome, microbiome and metaproteomic datasets from samples collected before and after the onset of islet autoimmunity in a cohort of children at risk of T1D. We show strong age-related effects across all three ‘omic datasets. Mastadenovirus infection was linked to profound functional changes in the metaproteome. Multiomic factor analysis modelling revealed proteins derived from the genus Faecalibacterium were linked to case-control status. The methods we have developed form a framework for future large-scale studies investigating disease progression in the context of an altered host-microbe relationship.