Dysbiosis of bacterial and fungal microbiomes affects the disease process and treatment outcome in fungal keratitis.

Fungal keratitis (FK) is a severe eye infection mainly caused by Aspergillus flavus and Fusarium solani. We examined the changes in bacterial and fungal microbiome profiles over a week of disease progression, treatment, and clinical status using targeted next-generation sequencing (NGS). Samples were collected from infected and healthy contralateral eyes of 25 FK patients and one eye of 10 healthy, non-infected cataract controls. QIIME (Quantitative Insights into Microbial Ecology) and MicrobiomeAnalyst were utilised for the data analysis. There was a reduction in beneficial bacteria like Prevotella, Lactobacillus, and Leuconostoc in FK patients compared to the control samples. On the other hand, opportunistic bacteria including Clostridium, Bifidobacterium, and Pseudomonas increased in FK patients. Aspergillus, Colletotrichum, and Basidiobolus were more abundant in keratitis patients, whereas Malassezia and Trichoderma were less abundant. This dysbiosis was also evident in the uninfected contralateral eyes of FK patients. Treatment resulted in significant changes in bacterial genera like Dolosigranulum, Sutterella, and Akkermansia, and fungal genera such as Myrothecium, Corynespora, and Penicillium. Further, treatment returned them to the control group levels, except for Akkermansia and Corynespora. Among the treated patients, a large subset remains nonresponsive to treatment. This treatment outcome, responder versus non-responder, was reflected in the abundance of bacterial genera such as Tannerella, Sutterella, Odoribacter, and fungal genera such as Coprinellus and Volutella. This study highlights the clinical relevance of microbiome signatures in FK, demonstrating bilateral dysbiosis, integrated bacterial-fungal profiling, and correlations with treatment outcomes. These findings suggest potential for microbiome-informed diagnostics, prognostic biomarkers, and risk stratification.