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GutMGene-Guided Peripheral Blood Transcriptomics Identifies an FLNA-Associated Host-Gene Signal in Diabetic
Chuanxue Ma1, Yujun Wang1, Yi Liu1
1Nanjing Hospital of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China.
International Journal of Molecular Sciences
|July 28, 2026
Summary
Diabetic retinopathy (DR) is linked to gut microbes and metabolites. Filamin A (FLNA) emerged as a key gene connecting these factors to immune and vascular changes in DR.
Area of Science:
- Genomics
- Microbiome research
- Ophthalmology
Background:
- Diabetic retinopathy (DR) involves retinal microvascular damage and systemic immune-metabolic stress.
- Existing DR transcriptomic data often lacks paired microbiome and metabolomic profiles.
- Understanding the gut-host-retina axis is crucial for DR pathogenesis.
Purpose of the Study:
- To identify host genes linking gut microbiome/metabolite data to DR.
- To investigate the role of candidate genes in DR-associated immune and vascular changes.
- To pinpoint specific host response signals in DR.
Main Methods:
- Integrated gutMGene v2.0 microbe/metabolite-host gene prior with peripheral blood transcriptomics (GSE221521).
- Employed weighted gene co-expression network analysis (WGCNA), resampling, and cross-dataset validation.
- Utilized single-cell localization and gene regulatory network (GRN) virtual knockout for filamin A (FLNA).
Main Results:
- Ten gut microbe and microbial metabolite-related genes (GMMRGs) were identified, with FLNA prioritized.
- FLNA signal was strongest in type 2 diabetes (T2D) PBMCs, retinal endothelial cells, and proliferative DR with diabetic macular edema (PDR + DME) retinal tissue.
- FLNA virtual knockout predicted cell-context-specific immune perturbations, including IL4R in B cells and CTSD in monocytes/NK cells.
Conclusions:
- FLNA is a significant circulating host-response gene in DR.
- This study establishes a link between curated microbe/metabolite-host records and DR pathophysiology.
- FLNA connects gut microbial influences to immune-vascular and cytoskeletal remodeling in DR.
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