1. Academic Validation
  2. Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice

Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice

  • Sci Rep. 2021 Mar 17;11(1):6094. doi: 10.1038/s41598-021-85681-w.
Jeon-Kyung Kim  # 1 Sang-Kap Han  # 1 Min-Kyung Joo 1 Dong-Hyun Kim 2
Affiliations

Affiliations

  • 1 Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, South Korea.
  • 2 Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, South Korea. dhkim@khu.ac.kr.
  • # Contributed equally.
Abstract

Gut microbiota regulate the neurodevelopmental processes and brain functions through the regulation of the microbiota-gut interaction and gut-brain communication. Buspirone, an agonist for serotonin 5-HT1A receptors, is used for the treatment of anxiety/depression. Therefore, to understand the gut microbiota-mediated mechanism of buspirone on anxiety/depression, we examined its effect on the immobilization stress (IS) or Escherichia coli K1 (EC)-induced anxiety/depression in mice. Oral or intraperitoneal administration of buspirone significantly suppressed stressor-induced anxiety/depression-like behaviors in the elevated plus maze, LIGHT/dark transition, tail suspension, and forced swimming tasks. Their treatments also reduced TNF-α expression and NF-κB+/Iba1+ cell population in the hippocampus and myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon. Buspirone treatments partially restored IS- or EC-induced gut microbiota perturbation such as β-diversity to those of normal control mice: they reduced the IS- or EC-induced gut Proteobacteria population. In particular, the anxiolytic activity of buspirone was positively correlated with the populations of Bacteroides and PAC001066_g in EC- or IS-exposed mice, while the populations of Lachnospiraceae, KE159660_g, LLKB_g, Helicobacter, and PAC001228_g were negatively correlated. The anti-depressant effect of buspirone was positively correlated with the Roseburia population. The fecal microbiota transplantations from buspirone-treated mice with IS-induced anxiety/depression or normal control mice suppressed IS-induced anxiety/depression-like behaviors and reduced hippocampal NF-κB+/Iba1+ and colonic NF-κB+/CD11c+ cell populations in the transplanted mice. Furthermore, they modified IS-induced perturbation of gut microbiota composition, particularly Proteobacteria, in the transplanted mice. In conclusion, buspirone alleviates IS as well as EC-induced anxiety/depression and colitis. It also suppresses associated neuroinflammation and modulates gut microbiota. Future studies can help to explain the relationship, if any, in the central and peripheral effects of buspirone.

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