Reshaped commensal wound microbiome via topical application of Calvatia gigantea extract contributes to faster diabetic wound healing

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Abstract
Calvatia gigantea (CG) is widely used as a traditional Chinese medicine for wound treatment. In this study, we aimed to determine the effects of CG extract (CGE) on diabetic wound healing and the commensal wound microbiome. A wound model was established using leptin receptor-deficient db/db mice, with untreated mice as the control group and CGE-treated mice as the treatment group. The wound healing rate, inflammation and histology were analyzed. Additionally, wound microbiome was evaluated via 16S ribosomal RNA (rRNA) gene sequencing. CGE significantly accelerated the healing of diabetic ulcer wounds, facilitated re-epithelialization, and downregulated the transcription levels of the inflammatory cytokines, interleukin-1β and tumor necrosis factor-α. Furthermore, CGE treatment positively affected the wound microbiome, promoting diversity of the microbial community and enrichment of Escherichia–Shigella bacteria in the CGE-treated group. Overall, CGE enhanced diabetic wound healing by modulating the wound microbiome and facilitating macrophage polarization during inflammation. These findings suggest modulation of the commensal wound microbiome using medicinal plants as a potential therapeutic strategy for diabetic wounds.
Funding Information
  • National Natural Science Foundation of China (82372521, 82172217, 82003305)
  • Jiangsu Province Traditional Chinese Medicine Development Project (MS2022006)
  • Natural Science Research Project of the Jiangsu Higher Education Institutions of China (22KJA360002)
  • Natural Science Foundation of Nanjing University of Chinese Medicine (XZR2020048, XZR2020069)
  • Key Science and Technology Program Projects of Jinhua Science and Technology Bureau (2022-3-147)
  • Graduate Student Scientific Research Innovation Projects in Jiangsu Province (SJCX23_0743)
  • College Student Innovation Training Program (103152023164, 202210315057Y)

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