Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice

Abstract

Abstract Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D + ) or without depression (IBD/D − ), we analyzed the fecal microbiota composition of patients with IBD with (/D + ) or without depression (/D − ) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D + or IBD/D − caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB + /CD11c + cell population in the colon. Transplantation of the IBD/D + patient feces (IBD/D + -F) caused IBD-like colitis more strongly than that of IBD/D − -F. FMTs from patients with IBD/D + also caused anxiety-/depression-like behaviors, increased the NF-κB + /Iba1 + and lipopolysaccharide (LPS) + /Iba1 + cell populations, and decreased the BDNF + /NeuN + cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D − caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D + -F vs. IBD/D − -F. However, the transplantation of HV-F into mice previously transplanted with IBD/D + -F significantly reduced depression-like behaviors, NF-κB + /Iba1 + and LPS + /Iba1 + cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.