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.

Highlights

  • The development of vision in newborns is incomplete and affected by external factors, such as a lack of nutrients, the overuse of drugs, and stimulation by high-intensity light

  • Using the black retinal pigment epithelium (RPE), we identified the spatial range of the cornea and found that the corneal area in Abxtreated mice was smaller than that of control mice at P21 and P28 (Fig. 1c)

  • We found that the continuous use of Abxs caused dysbiosis of the gut microbiota in neonatal mice and impaired their corneal development through the alteration of the corneal gene transcription, and decreases in the corneal area and thickness, the area of limbal blood vessels, the length and density of corneal nerve fibers, and the proportion of CCR2− corneal macrophages

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Summary

Introduction

The development of vision in newborns is incomplete and affected by external factors, such as a lack of nutrients, the overuse of drugs, and stimulation by high-intensity light These adverse factors may cause the abnormal development of the eyeballs and the alteration of neurogenesis, permanently impairing vision.[1] The cornea is located at the anterior segment of the eye and is responsible for nearly two-thirds of the refractive power of the optic axis. The area of the limbal blood vessels gradually increases after birth and reaches the level of an adult mouse’s cornea at P21.9,10 Nerve fibers first grow into the anterior segment and the corneal stroma from four directions at E12.5─13.5 and innervate the epithelium at E16.5 These epithelial nerve fibers gather at the corneal center to form the typical vortex at P21.11

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