Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Microbiome-guided prioritization of Corynebacterium striatum in diabetic foot ulcers and preclinical evaluation of tanshinone IIA.
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Zhao Yi'an, Zhao Xin, Lian Jiaqi, Wang Shengyu, Ning Qiuyi, Xu Qiuyu, Zhang Zhen, Zong Junwei, Wang Shouyu
Аннотация
BACKGROUND: Diabetic foot ulcers (DFUs) are characterized by impaired healing and infection, but microbial signatures linked to glycemic status and their therapeutic relevance remain unclear.
PURPOSE: To identify DFU taxa associated with glycemic status and test whether microbiome-guided prioritization can inform evaluation of Tanshinone IIA (Tan IIA).
STUDY DESIGN: Clinical metagenomic discovery followed by in vitro functional and multi-omics analyses, biophysical studies, and in vivo evaluation.
METHODS: Wound samples from 54 DFU patients underwent HbA1c-stratified shotgun metagenomics. A prioritized patient-derived Corynebacterium striatum isolate was assessed for Tan IIA antibacterial and antibiofilm activity, multi-omics responses, and candidate-protein binding. Topical Tan IIA was tested in non-inoculated and C. striatum-inoculated diabetic wounds.
RESULTS: C. striatum was enriched in higher-HbA1c wounds and positively associated with continuous HbA1c (β = 0.422, 95% CI 0.095-0.748; P = 0.011; q = 0.064). Tan IIA inhibited the isolate (MIC = 64 μ g/ml), reduced biofilm biomass, and induced stress, redox, cell-envelope, and metabolic responses. SPR supported binding to MurD and TrxB. On day 14, wound closure was significantly greater in inoculated wounds (93.40% vs. 78.80%; adjusted P = 0.0187). In inoculated wounds, Tan IIA reduced EUB338-positive bacterial signal and viable counts versus vehicle (8.587 vs. 8.847 log10 CFU/g; adjusted P = 0.0480).
CONCLUSION: HbA1c-stratified metagenomics prioritized C. striatum as a glycemic-status-associated candidate. These findings support microbiome-guided preclinical evaluation of plant-derived Tan IIA as a topical candidate for infected DFUs.
PURPOSE: To identify DFU taxa associated with glycemic status and test whether microbiome-guided prioritization can inform evaluation of Tanshinone IIA (Tan IIA).
STUDY DESIGN: Clinical metagenomic discovery followed by in vitro functional and multi-omics analyses, biophysical studies, and in vivo evaluation.
METHODS: Wound samples from 54 DFU patients underwent HbA1c-stratified shotgun metagenomics. A prioritized patient-derived Corynebacterium striatum isolate was assessed for Tan IIA antibacterial and antibiofilm activity, multi-omics responses, and candidate-protein binding. Topical Tan IIA was tested in non-inoculated and C. striatum-inoculated diabetic wounds.
RESULTS: C. striatum was enriched in higher-HbA1c wounds and positively associated with continuous HbA1c (β = 0.422, 95% CI 0.095-0.748; P = 0.011; q = 0.064). Tan IIA inhibited the isolate (MIC = 64 μ g/ml), reduced biofilm biomass, and induced stress, redox, cell-envelope, and metabolic responses. SPR supported binding to MurD and TrxB. On day 14, wound closure was significantly greater in inoculated wounds (93.40% vs. 78.80%; adjusted P = 0.0187). In inoculated wounds, Tan IIA reduced EUB338-positive bacterial signal and viable counts versus vehicle (8.587 vs. 8.847 log10 CFU/g; adjusted P = 0.0480).
CONCLUSION: HbA1c-stratified metagenomics prioritized C. striatum as a glycemic-status-associated candidate. These findings support microbiome-guided preclinical evaluation of plant-derived Tan IIA as a topical candidate for infected DFUs.