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

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.

Buspirone Ameliorates Colon Inflammation in TNBS-Induced Rat Acute Colitis: The Involvement of TLR4/NF-kB Pathway

“…They concluded that buspirone, by inhibiting inflammatory factors such as; TNF-α, IL-1β, and IL-6 reduced inflammation [43]. Another animal study in 2021 showed that buspirone inhibited inflammation and reduced colitis by inhibiting myeloperoxidase and NF-κB activation [14]. Buspirone can be effective in treating various inflammatory diseases such as colitis, psoriasis, and dermatitis that have elevated levels of TNF-α and other inflammatory factors [44].…”

“…Our study shows that buspirone reduces MPO expression and has lucrative effects in treating acute colitis 38 . Buspirone is an oral anti-anxiety drug mainly used to treat anxiety disorders, especially generalized anxiety disorder 14 . Our study is in accordance with the anti-inflammatory effect of buspirone.…”

“…Parallel with our findings, recent experimental studies on the anti-inflammatory properties of buspirone uncovered that buspirone exerts dual positive effects in the central and peripheral systems. Buspirone is able to attenuate anxiety and depression as well as colitis by modulating neuroinflammation and gut microbiota 45 46 . Also, studies have confirmed that IBD patients are at an increased risk of anxiety or depression.…”

“…Some investigations showed the anti-inflammatory effects of buspirone through the reduction of NF-κB and some inflammatory cytokines such as TNF-α and IL-1β [13]. Buspirone treatment also reduced TNF-α expression and NF-κB activity in mice's hippocampus and colon tissues in an experimental model of anxiety/depression [14]. According to the established anti-inflammatory mechanisms of buspirone, this experiment aims to evaluate the anti-inflammatory activity of buspirone by reducing the TLR4/NF-κB signaling pathway in TNBS-induced rat colitis.…”

Effect of Systemic Administration of Amitriptyline on Oral Microbes in Rats

“…Recently, alterations in the intestinal flora caused by psychotropic drugs, including fluoxetine, AMI, and buspirone, have been shown in animal models (9,10). Alterations in the intestinal flora may be beneficial in improving depression and anxiety (10). It has not been shown how the oral flora is altered by the administration of psychotropic drugs.…”