Microorganisms in the gut have a role in regulating brain function, stress response and circadian rhythms. However, the integrated modulation of these three processes by the gut microbiota remains unclear. In this study, Tofani et al. highlight the gut microbiota as a crucial regulator of the stress–circadian axis.

Next, the authors performed transcriptomics of different brain regions — the suprachiasmatic nucleus in the hypothalamus, the hippocampus and the amygdala — that are important for circadian and stress regulation. The authors compared gene expression in those regions between germ-free mice, microbiota-depleted mice and conventional mice and identified several transcripts that lost rhythmicity. Particularly, changes in gut microbiota altered the clock machinery in the suprachiasmatic nucleus — the main circadian coordinator. Analysing the hippocampus and amygdala transcriptomes, the authors found that several transcripts that lost their rhythmicity were associated with stress functions in both regions, which indicates that the gut microbiota affects the rhythmicity of stress pathways in those brain regions that are key for stress response.