Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis

Cell Rep. 2016 May 31;15(9):1945-56. doi: 10.1016/j.celrep.2016.04.074. Epub 2016 May 19.

Abstract

Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6C(hi) monocytes in the brain than antibiotic-treated mice. Elimination of Ly6C(hi) monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6C(hi) monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6C(hi) monocytes.

MeSH terms

  • Adoptive Transfer
  • Aging / physiology*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antibiosis / drug effects
  • Antigens, Ly / metabolism*
  • Brain / drug effects
  • Brain / physiology
  • Cell Count
  • Cells, Cultured
  • Coculture Techniques
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / physiology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurogenesis / drug effects*
  • Physical Conditioning, Animal
  • Probiotics / pharmacology
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / drug effects

Substances

  • Anti-Bacterial Agents
  • Antigens, Ly
  • Ly-6C antigen, mouse