Bacteroides species differentially modulate depression-like behavior via gut-brain metabolic signaling

Gut microbiome disturbances have been widely implicated in major depressive disorder (MDD), although the identity of causal microbial species and the underlying mechanisms are yet to be fully elucidated. Here we show that Bacteroides species enriched in the gut microbiome from MDD patients differentially impact the susceptibility to depressive behaviors. Transplantation of fecal microbiome from MDD patients into antibiotic-treated mice induced anxiety and despair-like behavior and impaired hippocampal neurogenesis. Colonization of Bacteroides fragilis, Bacteroides uniformis, and, to a lesser extent, Bacteroides caccae, but not Bacteroides ovatus, recapitulated the negative effects of MDD microbiome on behavior and neurogenesis. The varying impacts of Bacteroides species were partially explained by differential alternations of tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. Notably, an intensified depletion of cerebral serotonin concurred with the enhanced susceptibility to depression. Together, these findings identify select Bacteroidetes species that contribute to depression susceptibility in mice by metabolic regulation along the gut-brain axis.

Automated summary

Disturbances in gut microbiome, particularly Bacteroides species, are implicated in major depressive disorder (MDD) susceptibility. This study demonstrates the differential impacts of Bacteroides fragilis, Bacteroides uniformis, Bacteroides caccae, and Bacteroides ovatus on depressive behavior and neurogenesis. The effects are partially mediated by alterations in tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. Moreover, the intensified depletion of cerebral serotonin is associated with increased susceptibility to depression.