Microbial, Metabolic, and Inflammatory Features Associated with Delayed Diabetic Wound Healing in Mice

Diabetic ulcers are characterized by delayed tissue repair, persistent inflammation, and wound microenvironment remodeling, yet the systemic and local molecular features associated with impaired diabetic wound healing remain incompletely defined.

In this exploratory pilot study, we profiled gut microbiota (16S rRNA sequencing), wound-tissue metabolites (liquid chromatography-mass spectrometry, LC-MS), and local gene expression (reverse transcription-quantitative polymerase chain reaction, RT-qPCR) in a mouse model of diabetic ulcers. Three biological replicates per group (n = 3 mice/group) were included in each analytical platform.

Compared with non-diabetic wound controls, diabetic mice showed delayed healing alongside altered gut microbial structures, including enrichment of Clostridiales and Mucispirillum and depletion of Lactobacillus. Wound metabolomics tentatively identified candidate metabolic shifts involving molecules such as 16-oxopalmitate and indoleacetaldehyde. Locally, candidate pro-inflammatory genes (Il1b, Tnf, Nos2, Mmp9) were upregulated, whereas candidate repair-associated markers (Arg1, Vegfa) were decreased. Correlation analysis further connected selected diabetes-associated microbial changes with local wound metabolic remodeling, revealing exploratory associations among gut microbial features, wound metabolites, and local inflammatory/repair-related gene expression in delayed diabetic wound healing.

In view of very small sample size (n = 3 per group), these findings provide hypothesis-generating preclinical evidence relevant to diabetic wound microenvironment remodeling, and indicates specific microbial, metabolic, and gene-expression targets for larger validation studies.