AbstractBackgroundThe probiotic potential of Lacticacid bacteria has been studied in various medical complications, from gastrointestinal diseases to antibiotic resistance infections recently. Moreover, diabetic ulcer (DU) is known as one of the most significant global healthcare concerns, which comprehensively impacts the quality of life for these patients.

摘要背景乳酸菌的益生菌潜力已被研究用于各种医学并发症，从胃肠道疾病到抗生素耐药性感染。此外，糖尿病性溃疡（DU）被认为是全球最重要的医疗保健问题之一，它全面影响这些患者的生活质量。

Given that the conventional treatments of DUs have failed to prevent later complications completely, developing alternative therapies seems to be crucial.MethodsWe designed the stable oleogel-based formulation of viable probiotic cells, including Lactobacillus rhamnosus (L. rhamnosus), Lactobacillus casei (L.

鉴于DUs的常规治疗未能完全预防后来的并发症，因此开发替代疗法似乎至关重要。方法我们设计了稳定的基于油凝胶的活益生菌细胞配方，包括鼠李糖乳杆菌（L.rhamnosus），干酪乳杆菌（L。

casei), Lactobacillus fermentum (L. fermentum), and Lactobacillus acidophilus (L. acidophilus) individually to investigate their effect on wound healing process as an in vivo study. The wound repair process was closely monitored regarding morphology, biochemical, and histopathological changes over two weeks and compared it with the effects of topical tetracycline as an antibiotic approach.

酪蛋白），发酵乳杆菌（发酵乳杆菌）和嗜酸乳杆菌（嗜酸乳杆菌）分别作为体内研究来研究它们对伤口愈合过程的影响。在两周内密切监测伤口修复过程的形态学，生化和组织病理学变化，并将其与局部四环素作为抗生素方法的效果进行比较。

Furthermore, the antibiofilm activity of probiotic bacteria was assessed against some common pathogens.ResultsThe findings indicated that all tested lactobacillus groups (excluded L. casei) included in the oleogel-based formulation revealed a high potential for repairing damaged skin due to the considerably more levels of hydroxyproline content of tissue samples along with the higher numerical density of mature fibroblasts cell and volume density of hair follicles, collagen fibrils, and neovascularization in comparison with antibiotic and control groups.

此外，针对一些常见病原体评估了益生菌的抗生物膜活性。结果研究结果表明，与抗生素组和对照组相比，基于油凝胶的制剂中包括的所有测试的乳杆菌组（不包括干酪乳杆菌）显示出修复受损皮肤的高潜力，因为组织样品中羟脯氨酸含量相当高，成熟成纤维细胞的数字密度较高，毛囊，胶原纤维和新血管形成的体积密度较高。

L. acidophilus and L. rhamnosus showed the best potential of wound healing among all lactobacillus species, groups treated by tetracycline and control groups. Besides, L. rha.

五十、 嗜酸乳杆菌和鼠李糖乳杆菌在所有乳酸杆菌物种，四环素治疗组和对照组中显示出最佳的伤口愈合潜力。此外，L.rha。

IntroductionThe wound healing cascade is a complex multicellular process that initiates at the moment of injury, involving four sequential phases of hemostasis: inflammatory, proliferative, and re-epithelialization [1]. Each phase includes events regulated by numerous physical and biochemical factors and fibroblasts, which play a crucial role in all phases, particularly in the proliferation step [2].

引言伤口愈合级联是一个复杂的多细胞过程，在受伤时开始，涉及止血的四个连续阶段：炎症，增殖和再上皮化（1）。每个阶段都包括由许多物理和生化因素以及成纤维细胞调节的事件，这些因素在所有阶段都起着至关重要的作用，特别是在增殖步骤中。

Vascular endothelial growth factor (VEGF) is one of the significant factors in the wound-healing process that contributes to angiogenesis, epithelialization, and collagen deposition [3]. As collagen is a central component of the extracellular matrix, it effectively takes part in the regulation of the wound repair process via inducing the platelets activation, resulting in fibrin clots at the injury site, promoting fibroblast proliferation in the inflammatory stage, synthesis of the growth factors associated with angiogenesis, matrix remodeling, and facilitation of re-epithelialization stage [4, 5].Diabetic ulcer (DU) pose a significant challenge to healthcare systems worldwide due to their increased rates of mortality and morbidity, as well as adversely impacting the health-related quality of life for patients with diabetes mellitus resulting from the complications of lower limb amputations [6].

血管内皮生长因子（VEGF）是伤口愈合过程中的重要因素之一，有助于血管生成，上皮化和胶原沉积（3）。由于胶原蛋白是细胞外基质的核心成分，它通过诱导血小板活化，在损伤部位产生纤维蛋白凝块，促进炎症阶段的成纤维细胞增殖，合成与血管生成，基质重塑和促进再上皮化阶段相关的生长因子，有效地参与伤口修复过程的调节[4，5]。糖尿病性溃疡（DU）由于其死亡率和发病率的增加，以及对下肢截肢并发症导致的糖尿病患者的健康相关生活质量产生不利影响，对全球医疗保健系统构成了重大挑战。

The conventional treatment of DU emphasizes wound debridement, off-loading of weight, and antibiotic therapy to control infection. In contrast, the ever-increasing failures of treatment response have been reported in these patients [7]. Antibiotic-resistant diseases are the common reasons for this failure in some cases of severe conditions despite receiving antibiotic therapy, which could raise the necessity of amputation surgeries [8].

DU的常规治疗强调伤口清创，减轻体重和抗生素治疗以控制感染。相比之下，这些患者的治疗反应失败率不断增加（7）。尽管接受了抗生素治疗，但在某些严重情况下，抗生素耐药性疾病是导致这种失败的常见原因，这可能会增加截肢手术的必要性（8）。

Therefore, some alternative approaches are cru.

因此，一些替代方法是cru。

Data availability

数据可用性

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

本研究中使用和/或分析的数据集可根据合理要求从通讯作者处获得。

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Download referencesFundingThis study was funded by Shiraz University of Medical Sciences (Grant number: 23627).Author informationAuthors and AffiliationsBiotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, IranFarkhonde Karimi, Nima Montazeri-Najafabady, Fatemeh Mohammadi & Ahmad GholamiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, IranFarkhonde Karimi & Ahmad GholamiEndocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, IranNima Montazeri-Najafabady & Farhad KoohpeymaDepartment of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranAmir AzadiAuthorsFarkhonde KarimiView author publicationsYou can also search for this author in.

。作者信息作者和附属机构设拉子医科大学生物技术研究中心，设拉子，IranFarkhonde Karimi，Nima Montazeri Najafabady，Fatemeh Mohammadi＆Ahmad GholamiDepartment of Pharmaceutical Biotechnology，Shiraz University of Medical Sciences，Shiraz，Fars，IranFarkhonde Karimi＆Ahmad Gholaminendocrine and Metabolication Research Center，设拉子医科大学设拉子，IranNima Montazeri Najafabady＆Farhad Koohpeymadpartment of Pharmaceutics，Shiraz University of Medical Sciences，Shiraz AZ，IranAmir AzadiAuthorsFarkhonde KarimiView作者出版物您也可以在中搜索该作者。

PubMed Google ScholarNima Montazeri-NajafabadyView author publicationsYou can also search for this author in

PubMed Google ScholarNima Montazeri NajafabadyView作者出版物您也可以在

PubMed Google ScholarFatemeh MohammadiView author publicationsYou can also search for this author in

PubMed Google ScholarFatemeh MohammadiView作者出版物您也可以在

PubMed Google ScholarAmir AzadiView author publicationsYou can also search for this author in

PubMed Google ScholarAmir AzadiView作者出版物您也可以在

PubMed Google ScholarFarhad KoohpeymaView author publicationsYou can also search for this author in

PubMed Google ScholarFarhad KoohpeymaView作者出版物您也可以在

PubMed Google ScholarAhmad GholamiView author publicationsYou can also search for this author in

PubMed Google ScholarAhmad GholamiView作者出版物您也可以在

PubMed Google ScholarContributionsAhmad Gholami, Nima Montazeri-Najafabady, and Amir Azadi were responsible for designing the protocol, writing the protocol and report. Farkhonde Karimi was responsible for conducting the search, screening potentially eligible studies, extracting and analyzing data, interpreting results, updating reference lists and creating ’Summary of findings’ tables.

PubMed谷歌学术贡献Sahmad Gholami，Nima Montazeri Najafabady和Amir Azadi负责设计协议，撰写协议和报告。Farkhonde Karimi负责进行搜索，筛选可能符合条件的研究，提取和分析数据，解释结果，更新参考列表并创建“结果摘要”表。

Also, Farkhonde Karimi and Fatemeh Mohammadi were responsible for writing the main manuscript text and prepared figures. Farhad Koohpeyma designing the protocol and screening potentially eligible studies. He contributed to writing the report, extracting and analyzing data, interpreting results and creating ’Summary of findings’ tables.

此外，Farkhonde Karimi和Fatemeh Mohammadi负责撰写主要手稿文本和准备数字。。他为撰写报告、提取和分析数据、解释结果和创建“调查结果摘要”表格做出了贡献。

He also contributed to data extraction. Ahmad Gholami, Nima Montazeri-Najafabady,and Amir Azadi provided feedback on the report.Corresponding authorCorrespondence to.

他还为数据提取做出了贡献。Ahmad Gholami、Nima Montazeri Najafabady和Amir Azadi对报告提供了反馈。对应作者对应。

Ahmad Gholami.Ethics declarations

Ahmad Gholami。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

。

Ethics approval and consent to participate

道德批准和同意参与

This study was approved locally by the Ethics Committee of Shiraz University of Medical Sciences (Code: ir.sums.aec.1400.027).

这项研究得到了设拉子医科大学伦理委员会的批准（代码：ir。sums。aec。1400.027）。

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Reprints and permissionsAbout this articleCite this articleKarimi, F., Montazeri-Najafabady, N., Mohammadi, F. et al. A potential therapeutic strategy of an innovative probiotic formulation toward topical treatment of diabetic ulcer: an in vivo study.

转载和许可本文引用本文Karimi，F.，Montazeri Najafabady，N.，Mohammadi，F。等人。创新益生菌制剂局部治疗糖尿病溃疡的潜在治疗策略：体内研究。

Nutr. Diabetes 14, 66 (2024). https://doi.org/10.1038/s41387-024-00320-3Download citationReceived: 29 November 2023Revised: 22 July 2024Accepted: 24 July 2024Published: 20 August 2024DOI: https://doi.org/10.1038/s41387-024-00320-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

营养。糖尿病14,66（2024）。https://doi.org/10.1038/s41387-024-00320-3Download引文接收日期：2023年11月29日修订日期：2024年7月22日接受日期：2024年7月24日发布日期：2024年8月20日OI：https://doi.org/10.1038/s41387-024-00320-3Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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