BACKGROUND: The gut microbiome has been linked to mood disorders via communication along the gut-brain axis. We previously found levels of fecal Bacteroides were inversely associated with brain signatures of depression in the prefrontal cortex of human subjects. Bacteroides are important human commensals, playing a keystone role in regulating the immune system and producing bioactive metabolites, like the neurotransmitter gamma-aminobutyric acid and B vitamins.
METHODS: To better understand the link between Bacteroides and depression - and test a candidate novel next-generation probiotic - we administered a human-derived Bacteroides salyersiae strain, HB32, orally in rats that were subjected to the repeated social defeat model of stress-induced depression. The fecal microbiome and the prefrontal cortex transcriptome were then profiled for intervention-induced alterations.
RESULTS: Orally delivered B. salyersiae HB32 reduced depressive-like behavior in male rats comparable to the drug ketamine, independently of the strain being administered in its viable or inactivated (iHB32) form. Mechanistically, we observed that stress-induced anhedonia required the vagus nerve for its phenotype to develop, suggesting crosstalk between the gut and the brain. In support of this, we found HB32 and iHB32, but not ketamine, rescued stress-induced differential expression patterns in the prefrontal cortex, including those related to serotonin signaling and oxidative stress. In the gut, prolonged exposure to social defeat led to broad shifts in the composition of the gut microbiome, with a predominant reduction of the endogenous Bacteroides. Administration of HB32, iHB32, and ketamine attenuated the impact of stress on the microbiome, and intake of live HB32 resulted in a significant increase of the B. salyersiae species in the fecal microbiome.
CONCLUSIONS: Depressive-like behavior in male rats induced by repeated social defeat requires vagal signaling, suggesting gut-brain-axis crosstalk. In animals with an intact vagus nerve, oral administration of viable or inactivated B. salyersiae HB32 reversed behavioral changes induced by chronic stress at levels comparable to ketamine. Additionally, supplementation of HB32 and iHB32 was associated with attenuation of stress-related microbiome and prefrontal cortex transcriptional changes.
Gut-Brain Axis