AUTHOR=Zhou Nian , Shi Liuju , Yuan Xiangke , Lang Jingyu , Wang Jixue , Li Jianpeng , Wang Yibo , Li Yanan 

TITLE=Uncovering the gut - skin axis: the role of specific traditional Chinese medicine interventions in regulating gut microbiota for diabetic foot ulcers and the analysis of research status

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1641036

DOI=10.3389/fphar.2025.1641036

ISSN=1663-9812

ABSTRACT=Diabetic foot ulcers (DFU), a severe complication of diabetes, are closely linked to gut-skin axis dysregulation, including gut microbiota imbalance, systemic inflammation, and impaired skin barrier function. This review highlights the potential of specific TCM interventions, including special traditional Chinese medicine preparations and acupuncture, in modulating this axis to treat DFU. The botanical drugs (e.g., Astragalus membranaceus Bunge (Milkvetch root, Fabaceae; official drug name: Huangqi), Paeonia lactiflora Pall. (Peony root, Paeoniaceae; official drug name: Baishao) and botanical drugs formulas (e.g., Jinhuang Powder, Simiao Yong’an Decoction) regulate gut microbiota to increase short-chain fatty acids (SCFAs), reduce pro-inflammatory cytokines (IL-1β, TNF-α), and enhance intestinal barrier integrity via tight junction proteins (ZO-1, claudin-1). Acupuncture, through techniques like encircling needling and moxibustion, improves microcirculation in lower limbs, activates the vagus nerve-anti-inflammatory pathway, and promotes SCFA production to alleviate inflammation and accelerate wound healing. Mechanisms involve multi-target regulation of Wnt/β-catenin, PI3K/AKT, and Nrf2 signaling pathways to enhance angiogenesis, collagen synthesis, and epidermal stem cell proliferation. The ability of special traditional Chinese medicine preparations and acupuncture to solve intestinal microbiota imbalance and skin repair provides a novel comprehensive strategy for DFU management, which is worth conducting large-scale clinical trials to verify its efficacy and safety. This review also evaluates the current evidence gaps, including small sample sizes in clinical trials and inconsistent preparation standards, which need to be addressed in future research.