Interactions between the gut microbiome and the brain affect mood and behaviour in health and disease. Using preclinical animal models, recent discoveries begin to explain how bacteria in the gut influence our mood as well as highlighting new findings relevant to autism. Autism-associated gene mutations known to alter synapse function in the CNS also affect inflammatory response and modify the enteric nervous system resulting in abnormal gastrointestinal motility and structure. Strikingly, these mutations additionally affect the gut microbiome in mice. This review describes the changes in gut physiology and microbiota in mouse models of autism with modified synapse function. The rationale for different regions of the gastrointestinal tract having variable susceptibility to dysfunction is also discussed. To dissect underlying biological mechanisms involving gut-brain axis dysfunction in preclinical models, a range of multidisciplinary approaches are required. This research will provide insights into the role of the gut-brain axis in health and neurodevelopmental disorders including autism.