Antibiotic-induced dysbiosis of gut microbiota impairs corneal development in postnatal mice by affecting CCR2 negative macrophage distribution

Mucosal Immunol. 2020 Jan;13(1):47-63. doi: 10.1038/s41385-019-0193-x. Epub 2019 Aug 21.

Abstract

Antibiotics are extremely useful, but they can cause adverse impacts on host bodies. We found that antibiotic treatment altered the composition of the gut microbiota and the gene expression profile in the corneal tissues of postnatal mice and decreased the corneal size and thickness, the angiogenesis of limbal blood vessels, and the neurogenesis of corneal nerve fibers. The reconstitution of the gut microbiota with fecal transplants in antibiotic-treated mice largely reversed these impairments in corneal development. Furthermore, C-C chemokine receptor type 2 negative (CCR2-) macrophages were confirmed to participate in corneal development, and their distribution in the cornea was regulated by the gut microbiota. We propose that the CCR2- macrophage population is a crucial mediator through which gut microbiota affect corneal development in postnatal mice. In addition, probiotics were shown to have the potential effect of restoring corneal development in antibiotic-treated mice. Abx-induced gut dysbiosis has significant, long-term effects on the development of the cornea, and reversal of these suppressive effects takes a long time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Cell Movement
  • Cells, Cultured
  • Cornea / physiology*
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Dysbiosis / etiology
  • Dysbiosis / immunology*
  • Fecal Microbiota Transplantation
  • Female
  • Gastrointestinal Microbiome / genetics*
  • Humans
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Postnatal Care
  • RNA, Ribosomal, 16S / genetics*
  • Receptors, CCR2 / metabolism

Substances

  • Anti-Bacterial Agents
  • Ccr2 protein, mouse
  • RNA, Ribosomal, 16S
  • Receptors, CCR2