Mapping gene expression across the microbiome–gut–brain axis of germ-free and specific pathogen-free mice

Perturbation of the gut microbiota has been implicated in neurological diseases via communication across the microbiome–gut–brain axis. As a result, the discovery of mechanisms underlying interaction across this axis is becoming increasingly important. The germ-free (GF) mouse model has enabled an improved understanding of the influence of the gut microbiota on brain development and function. By utilizing an advanced spatial profiling approach, we determined transcriptional changes in the brain, improving our understanding of how brain cells function and interact within their microenvironment in the absence of microbiome influence. Targeted regions of interest were selected based on brain regions implicated in neurological disease or reported structural differences between GF mouse brains and those of colonized mice. In the hippocampus, 276 differentially expressed genes (DEGs) were identified, 345 DEGs in the thalamus and 21 DEGs in the pons. Contrastingly, we identified only 2 DEGs in the midbrain and 4 in the medulla oblongata, with no DEGs in the cerebellum or corpus callosum. These data provide an overview of gut microbiota influence on gene expression in the brain, highlighting multiple genes of interest for further investigation in the context of microbiome influence on brain function and their potential relevance to neurological disease.