Antibiotic-Induced Dysbiosis of Gut Microbiota Impairs Corneal Nerve Regeneration by Affecting CCR2-Negative Macrophage Distribution

Am J Pathol. 2018 Dec;188(12):2786-2799. doi: 10.1016/j.ajpath.2018.08.009.


Although antibiotics are useful, they can also bring negative effects. We found that antibiotic-treated mice exhibit an alteration in the gene expression profile of corneal tissues and a decrease in corneal nerve density. During corneal wound healing, antibiotic treatment was found to impair corneal nerve regeneration, an effect that could be largely reversed by reconstitution of the gut microbiota via fecal transplant. Furthermore, CCR2- corneal macrophages were found to participate in the repair of damaged corneal nerves, and a decrease in CCR2- corneal macrophages in antibiotic-treated mice, which could be reversed by fecal transplant, was observed. Adoptive transfer of CCR2- corneal macrophages promoted corneal nerve regeneration in antibiotic-treated mice. The application of probiotics after administration of antibiotics also restored the proportion of CCR2- corneal macrophages and increased the regeneration of corneal nerve fibers after epithelial abrasion. These results suggest that dysbiosis of the gut microbiota induced by antibiotic treatment impairs corneal nerve regeneration by affecting CCR2- macrophage distribution in the cornea. This study also indicates the potential of probiotics as a therapeutic strategy for promoting the regeneration of damaged corneal nerve fibers when the gut microbiota is in dysbiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Cells, Cultured
  • Corneal Injuries / etiology*
  • Corneal Injuries / metabolism
  • Corneal Injuries / pathology
  • Disease Models, Animal
  • Dysbiosis / chemically induced
  • Dysbiosis / complications*
  • Dysbiosis / metabolism
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / immunology*
  • Receptors, CCR2 / physiology*
  • Wound Healing


  • Anti-Bacterial Agents
  • Ccr2 protein, mouse
  • Receptors, CCR2