Impact of broad-spectrum antibiotics on the gut-microbiota-spleen-brain axis

Xiayun Wan; Akifumi Eguchi; Akemi Sakamoto; Yuko Fujita; Yong Yang; Youge Qu; Masahiko Hatano; Chisato Mori; Kenji Hashimoto

doi:10.1016/j.bbih.2022.100573

Impact of broad-spectrum antibiotics on the gut-microbiota-spleen-brain axis

Brain Behav Immun Health. 2022 Dec 17:27:100573. doi: 10.1016/j.bbih.2022.100573. eCollection 2023 Feb.

Authors

Xiayun Wan¹, Akifumi Eguchi², Akemi Sakamoto³, Yuko Fujita¹, Yong Yang¹, Youge Qu¹, Masahiko Hatano³, Chisato Mori^{2

4}, Kenji Hashimoto¹

Affiliations

¹ Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan.
² Department of Sustainable Health Science, Chiba University Center for Preventive Medical Sciences, Chiba, 263-8522, Japan.
³ Department of Biomedical Science, Chiba University Graduate School of Medicine, Chiba, 260-8670, Japan.
⁴ Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.

Abstract

The spleen is a key immune-related organ that plays a role in communication between the brain and the immune system through the brain-spleen axis and brain-gut-microbiota axis. However, how the gut microbiota affects spleen and brain function remains unclear. Here, we investigated whether microbiome depletion induced by administration of an antibiotic cocktail (ABX) affects spleen and brain function. Treatment with ABX for 14 days resulted in a significant decrease in spleen weight and significant alterations in splenic functions, including the percentage of neutrophils, NK cells, macrophages, and CD8⁺ T cells. Furthermore, ABX treatment resulted in the depletion of a large portion of the gut microbiota. Untargeted metabolomics analysis showed that ABX treatment caused alterations in the levels of certain compounds in the plasma, spleen, and brain. Moreover, ABX treatment decreased the expression of microglia marker Iba1 in the cerebral cortex. Interestingly, correlations were found between the abundance of different microbiome components and metabolites in various tissues, as well as splenic cell populations and spleen weight. These findings suggest that ABX-induced microbiome depletion and altered metabolite levels may affect spleen and brain function through the gut-microbiota-spleen-brain axis.

Keywords: ABX, antibiotic cocktail; Brain-gut-microbiota axis; Brain-spleen axis; CNS, central nervous system; FDR, false discovery rate; GF, germ free; GFAP, glial fibrillary acidic protein; Metabolite; Microglia; OPLS-DA, orthogonal partial least squares discriminant analysis; VIP, variable importance in projection.