We mapped brain regions that are rapidly recruited in response to bacterial signals from the gut, examined the neuronal response following acute versus long-term signalling, and investigated the pathways that transmit these signals to distinct brain regions.

Intestinal bacteria interact with the brain via the ‘gut-brain axis’. Signalling along these pathways influences anxiety- and depression-like behaviours, along with central nervous system physiology under normal conditions and in states of stress and inflammation.

Male Balb/c mice were orally administered a single dose of saline or a live or heat-killed preparation of a physiologically active bacteria, Lactobacillus rhamnosus (JB-1). 165 minutes later, depression-like behaviour was measured, mesenteric vagal afferent fibre firing was recorded, and brain c-Fos immunoreactivity was mapped. Mice underwent sub-diaphragmatic vagotomy to investigate whether severing the vagus prevented JB-1-induced c-Fos expression. Finally, we examined the ΔFosB response and depression-like behaviour following acute versus chronic bacterial treatment.

Live, but not heat-killed bacteria significantly induced c-Fos expression in the basolateral and central amygdala, ventral hippocampus, periaqueductal grey, dorsal raphe nucleus, and locus coeruleus. Both live and heat-killed bacteria increased c-Fos expression in the paraventricular nucleus of the thalamus and facilitated firing of vagal fibres, absent behavioural changes. Severing the vagus prevented JB-1-induced c-Fos immunoreactivity in all regions except the ventral hippocampus and dorsal raphe nucleus. Only chronic, not acute treatment induced widespread ΔFosB in distributed brain regions, some of which previously exhibited no c-Fos response to a single dose.

These data identify regions that respond to bacteria-derived signals and highlight the differential response to acute versus chronic treatment. Moreover, the data suggest that the vagus nerve is critical for the widespread c-Fos response but also indicate the recruitment of additional signalling pathways. Future research will need to identify the gene targets of Fos proteins and their role in the observed behavioural changes.