Eye surface microbes shift dramatically in neurotrophic keratitis patients

People with neurotrophic keratitis, a rare corneal disease in which damage to sensory nerves leaves the eye surface poorly protected and slow to heal, carry a markedly different community of bacteria on the ocular surface than healthy people do. A new study from researchers at a Chinese eye center used bacterial gene sequencing to map those differences, and the results suggest the disease is accompanied not only by a shift in which microbes are present but also by a change in what those microbes are predicted to be doing metabolically.

The team enrolled 15 patients with neurotrophic keratitis and 30 healthy controls. Each participant provided a swab from the conjunctival fornix, the recessed pocket where the eyelid meets the eyeball, and the bacterial DNA was analyzed with 16S rRNA gene amplicon sequencing. Bioinformatic analyses included alpha and beta diversity measures, linear discriminant analysis effect size, known as LEfSe, to pinpoint taxa distinguishing the groups, and PICRUSt2 functional annotation to predict the metabolic capacities of the microbial communities from their gene content.

Compared with healthy controls, patients showed significantly elevated alpha diversity, meaning their ocular surface bacterial communities contained more species or a more even distribution across species. Beta diversity analysis revealed distinct clustering patterns, indicating that the bacterial profiles of patients were recognizably different from those of healthy eyes.

Compositional analysis identified 61 taxa at the phylum level. Among these, the relative abundance of Proteobacteria, a phylum that includes many Gram-negative organisms and is often a dominant component of the healthy ocular surface, was markedly decreased in the patient group. At the genus level, the study detected 1,251 taxa.

The LEfSe analysis screened out a set of genera serving as key biomarkers for the disease: Acinetobacter, Cutibacterium, Staphylococcus, Corynebacterium and Methylobacterium-Methylorubrum. Several are familiar residents of skin and mucosal surfaces, and their relative enrichment suggests the altered environment of a denervated, poorly healing cornea favors a different mix of colonizers than the healthy eye does. These are differences in relative abundance detected by sequencing, not proof that any of these organisms causes the disease.

The functional prediction step was perhaps the most striking part. Using PICRUSt2, the researchers estimated the metabolic pathways the ocular surface microbes could perform, and they found widespread reductions in the predicted abundance of core metabolic pathways in patients. These included fatty acid biosynthesis, aromatic amino acid biosynthesis, the tricarboxylic acid cycle, the central hub of cellular energy metabolism, and UDP-N-acetylglucosamine biosynthesis, which feeds into production of cell wall and glycan components. In other words, the microbial community in neurotrophic keratitis appears to have lost much of its predicted capacity for basic housekeeping metabolism.

At the same time, pathways related to branched-chain amino acid biosynthesis and unsaturated fatty acid metabolism were significantly enriched in the patient group. The authors interpret this pattern as a shift from suppressed core metabolism to elevated adaptive metabolism, possibly reflecting adaptation to the changed nutrient and inflammatory environment of the diseased eye surface. Because these functional profiles are predictions inferred from gene content rather than direct measurements of metabolic activity, they should be read as a hypothesis-generating map of what the microbes are equipped to do.

The study is explicitly preliminary. With 15 patients and 30 controls, it is a small cross-sectional comparison, and 16S amplicon sequencing leaves viruses, fungi and other ocular surface residents unexamined. The authors describe their work as a first link between ocular surface pathological changes in neurotrophic keratitis and the ocular surface microbiome, and frame the characteristic metabolic profile as a theoretical basis for further mechanistic research and clinical management rather than an immediate diagnostic or therapeutic tool.

Subject of Research: Ocular surface microbiome differences in neurotrophic keratitis patients

Article Title: Analysis of ocular surface microbiome characteristics in patients with neurotrophic keratitis

Article References: Lin, J., Wang, B., Liu, T., Sun, C., Zhang, H., & Jin, X. (2026). Analysis of ocular surface microbiome characteristics in patients with neurotrophic keratitis. BMC Microbiology. https://doi.org/10.1186/s12866-026-05892-x

Image Credits: AI Generated

DOI: 10.1186/s12866-026-05892-x

Keywords: neurotrophic keratitis, ocular surface microbiome, 16S rRNA sequencing, Proteobacteria, LEfSe biomarkers, PICRUSt2, metabolic pathways, alpha diversity, corneal disease, conjunctival swabs, Analysis, ocular