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Background Immunopathological concepts have been intensively discussed for schizophrenia. The polyriboinosinic-polyribocytidylic (PolyI:C) mouse model has been well validated to invasively study this disease. The intestinal microbiome exhibits broad immunological and neuronal activities. The relevance of microbiome alterations in the PolyI:C model to human schizophrenia should be explored. Methods Feces of offspring from mice mothers, who were administered to PolyI:C or NaCl (controls) at ED 9, were collected at PND 30 and 180 (PolyI:C and control mice (N = 32 each; half males and females). This was analyzed for bacterial 16S ribosomal DNA (rDNA) using a gut microbiome polymerase chain reaction (PCR) microarray tool. Results Differences were found in species richness of microbiome between animals of different ages (PND 30 and 180), but also between offspring from PolyI:C vs. NaCl treated mothers. In female mice at PND 30, the abundance of Prevotellaceae and Porphyromonadaceae was lower and that of Lactobacillales was higher, whereas in male mice at the same time point the abundance of four families of the Firmicutes phylum (Clostridia vadinBB60 group, Clostridiales Family XIII, Ruminococcaceae and Erysipelotrichaceae) was increased relative to the control group. Limitations No further analyses of cell types or cytokines involved in autoimmune gut and brain processes. Conclusions These finding seem to be similar to microbiome disturbances in patients with schizophrenia. The differential bacterial findings at day 30 (i.e., similar to the prodromal phase in patients with schizophrenia) correspond to the tremendous activation of the immune system with a strong increase in microglial cells which might be responsible for neuroplasticity reduction in cortical areas in patients with schizophrenia., (Copyright © 2021 Elsevier Inc. All rights reserved.)