There is a growing realization that the severity of the core symptoms of autism spectrum disorders and schizophrenia is associated with gastrointestinal dysfunction. Nonetheless, the mechanisms underlying such comorbidities remain unknown. Several genetic and environmental factors have been linked to a higher susceptibility to neurodevelopmental abnormalities. The maternal immune activation (MIA) rodent model is a valuable tool for elucidating the basis of this interaction. We induced MIA with polyinosinic–polycytidylic acid (poly I:C) at gestational day 12.5 and assessed behavioural, physiological and molecular aspects relevant to the gut–brain axis in the offspring of an outbred (NIH Swiss) and an inbred (C57BL6/J) mouse strain. Our results showed that the specific MIA protocol employed induces social deficits in both strains. However, alterations in anxiety and depression-like behaviours were more pronounced in NIH Swiss mice. These strain-specific behavioural effects in the NIH Swiss mice were associated with marked changes in important components of gut–brain axis communication: the endocrine response to stress and gut permeability. In addition, MIA-induced changes in vasopressin receptor 1a mRNA expression in the hypothalamus were observed in NIH Swiss mice only. Taken together, these data suggest that genetic background is a critical factor in susceptibility to the gut–brain axis effects induced by MIA.