|
1
|
Mekadim C, Mrazek J, Fliegerová KO, Sechovcová H, Mahayri TM, Jarošíková R, Husáková J, Wosková V, Tůma P, Polák J, Sojáková D, Němcová A, Dubský M, Fejfarová V. The effect of the administration form of antibiotic therapy on the gut microbiome in patients with infected diabetic foot ulcers - DFIATIM trial. BMC Microbiol 2025; 25:339. [PMID: 40437354 PMCID: PMC12117690 DOI: 10.1186/s12866-025-04041-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 05/12/2025] [Indexed: 06/01/2025] Open
Abstract
BACKGROUND Diabetic foot infections (DFIs) contribute to the global disability burden. Beta-lactams are the most commonly used antibiotics for treating DFIs. However, the use of antibiotics may lead to disruption of the healthy balance of the gut microbiota, causing dysbiosis. METHODS Patients with infected diabetic foot ulcers (iDFUs) were treated with two kinds of beta-lactams (amoxicillin/clavulanic acid or ceftazidime) according to microbial sensitivity of causative agents via bolus or continuous administration modes. Changes in the gut microbiome of patients were analyzed. Diabetic patients without iDFUs were used as a control group. 16 S ribosomal RNA gene amplicon sequencing was performed on stool samples collected from participants. RESULTS Alpha diversity and beta diversity of gut microbiota of treated patients did not show significant differences between bolus and continuous modes. However, significant differences were observed between gut microbiota diversity of treated patients and control group. PCoA plots showed individualized responses of the patient's gut microbiota to antibiotics at different times using both administration forms associated with the pre-treatment state of microbiota composition. Enterococcus, Sellimonas, and Lachnoclostridium were the common bacterial markers differentially abundant in the gut microbiota of antibiotic-treated patients with iDFUs while Roseburia, Dorea, and Monoglobus were mainly abundant in the gut microbiota of patients without iDFUs. Predicted pathways like "Transporters", "ABC transporters" and "Phosphotranspherase system (PTS)" were upregulated in the gut microbiome of patients treated with bolus regime which may lead to increased intestinal barrier permeability. CONCLUSION The present study reported alterations in gut microbiota composition and functionality and provided the bacterial markers as well as potential metabolic signatures associated with each administration mode in patients with iDFUs, which may be used as a reference set for future studies of the effect of antibiotics administration on the gut microbiome of patients with iDFUs. This study shed light on the importance of understanding the effect of antibiotic administration form on gut microbiome in patients with iDFUs. TRIAL REGISTRATION The DFIATIM Clinical Trial (Full title: "Rationalisation of ATB therapy in diabetic foot infection and its impact on the intestinal microbiota") is submitted to the European Union Clinical Trials Database under the EudraCT Number: 2019-001997-27. The date of registration is July 17th, 2020.
Collapse
Affiliation(s)
- Chahrazed Mekadim
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic.
| | - Jakub Mrazek
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Kateřina Olša Fliegerová
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Hana Sechovcová
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Tiziana Maria Mahayri
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Radka Jarošíková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Internal Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jitka Husáková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Veronika Wosková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Petr Tůma
- Department of Hygiene, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jan Polák
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Dominika Sojáková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Andrea Němcová
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Michal Dubský
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Vladimíra Fejfarová
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Internal Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| |
Collapse
|
|
2
|
Huang Y, Tang Y, Zhao X, Xu M, Chen M. Novel insights into the role of gut microbiota and its metabolites in diabetic chronic wounds. FASEB J 2025; 39:e70316. [PMID: 39785136 DOI: 10.1096/fj.202401478rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 12/14/2024] [Accepted: 01/01/2025] [Indexed: 01/12/2025]
Abstract
Wounds in patients with diabetes present significant physical and economic challenges due to impaired healing and prolonged inflammation, exacerbated by complex interactions between microbes. Especially, the development and healing of diabetic foot ulcers (DFUs) remain an urgent clinical problem. The human gut harbors a vast microbial ecosystem comprising intestinal flora and their metabolic products. Recent advancements in research have illuminated the concept of the "gut-skin axis," revealing intricate relationships between gut microbiota, microbiota-derived metabolites, and various skin diseases, including DFUs. This review aims to unravel the formation and healing process of DFUs in the context of the gut-skin axis. We reviewed the current research progress worldwide regarding to the gut-skin axis, compared and discussed significant changes in the microbiota colonizing the skin and gut in patients with DFUs. The roles of microbiota-derived metabolites such as lipopolysaccharides, short-chain fatty acids, and trimethylamine-N-oxide in the development of DFUs are highlighted. We also reviewed treatment strategies currently employed in clinical practice and identified potential therapeutic targets such as probiotics for treating DFUs. The need for more comprehensive experimental designs to elucidate the intricate relationship between gut microbiota and its metabolites in the context of DFUs are therefore highlighted.
Collapse
Affiliation(s)
- Yixuan Huang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Ying Tang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Xiaotong Zhao
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Murong Xu
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| |
Collapse
|
|
3
|
Savitri IJ, Suprarahardiani SA, Ulinnuha LK, Prahasanti C, Wijaksana IKE, Ridwan RD, E DS, Aljunaid MA, Syed S, Abullais SS. TNF-α Expression and Plasma Cell and Macrophage Numbers in Traumatic Ulcers in a Rat Model Treated by Topical or Systemic Probiotic L. casei Shirota. Int J Med Sci 2025; 22:318-327. [PMID: 39781533 PMCID: PMC11704693 DOI: 10.7150/ijms.99156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 10/24/2024] [Indexed: 01/12/2025] Open
Abstract
Introduction: Live microorganisms, named probiotics, can improve overall physical well-being, particularly the oral cavity's health. L. casei Shirota, a popular probiotic, can influence the immune response by increasing the number of macrophages and plasma cells that play a role in traumatic ulcer healing. Aims: To determine the expression of tumor necrosis factor-alpha (TNF-α) and the varied number of plasma cells and macrophages on a traumatic ulcer animal model treated with topical or systemic administration of a probiotic L. casei Shirota. Material and Methods: Thirty-six healthy, 2-3-month-old male Rattus norvegicus weighing 175-250 gram, were designed into control and topical and systemic administration probiotic groups. The control group was treated with Aquadest 20 uL/20 gr, while topical probiotic and systemic administration probiotic groups were treated with 10,9x107 cells/kg, respectively. A heated round burnisher tip was used to traumatize the inferior incisive fornix labial area. After 3 or 7 days, the animal models were terminated. Immunohistochemical examination, Hematoxylin eosin staining, and statistical analysis were performed to analyze the expression of TNF-α and the number of plasma cells and macrophages. Results: The Mann-Whitney and Tukey HSD tests indicated significant differences (p < 0.05) in the results for the three groups. It was observed that topical administration provides more remarkable results than systemic administration for the expression of TNF-α, the number of plasma cells, and the number of macrophages. Conclusion: Topical administration of L. casei Shirota demonstrates better results than systemic administration for healing traumatic ulcers.
Collapse
Affiliation(s)
- Irma Josefina Savitri
- Department of Periodontology, Faculty of Dental Medicine, Universitas Airlangga Surabaya, Indonesia
- Research Center for Biomaterial and Tissue Engineering, Universitas Airlangga Surabaya, Indonesia
| | | | | | - Chiquita Prahasanti
- Department of Periodontology, Faculty of Dental Medicine, Universitas Airlangga Surabaya, Indonesia
| | - I Komang Evan Wijaksana
- Department of Periodontology, Faculty of Dental Medicine, Universitas Airlangga Surabaya, Indonesia
| | - Rini Devijanti Ridwan
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga Surabaya, Indonesia
| | - Diah Savitri E
- Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga Surabaya, Indonesia
| | - Mohammed Ahmed Aljunaid
- Lectures in Department of Oral and Dental Medicine, Faculty of Medicine, Taiz University, Taiz-Yemen
| | - Sadatullah Syed
- Diagnostic Dental Sciences, College of Dentistry, King Khalid University, 62529 Abha, Saudi Arabia
| | - Shahabe Saquib Abullais
- Central Labs, King Khalid University, AlQura'a, Abha, P.O. Box 960, Saudi Arabia
- Department of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, 62529 Abha, Saudi Arabia
| |
Collapse
|
|
4
|
Kord-Parijaee E, Ferdosi-Shahandashti E, Bakhshandeh B, Pournajaf A. Enhancing Gingival-Derived Mesenchymal Stem Cell Potential in Tissue Engineering and Regenerative Medicine Through Paraprobiotics. Tissue Eng Part C Methods 2024; 30:512-521. [PMID: 39165236 DOI: 10.1089/ten.tec.2024.0169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2024] Open
Abstract
Gingival-derived mesenchymal stem cells (GMSCs) stand for a unique source of mesenchymal stem cells (MSCs) isolated from a neural crest origin with potential application in regenerative medicine. However, there are some limitations to the usage of these cells in clinical cell therapy such as reduced cell number and undesirable differentiation of the cell throughout frequent passages. Nowadays, studies have applied manipulation strategies to improve MSCs' effectiveness in clinical therapy. Among all of the materials used for this purpose, there is a growing trend for the use of biomaterials such as probiotic extracts or their conditioned media due to their lower toxicity. In the present study, we utilized extracts from Lactobacillus reuteri and Lactobacillus rhamnosus to assess their potential to enhance the function of GMSCs. We compared the effectiveness of these bacterial extracts to determine their relative efficacy. Bacterial extracts of two lactic acid bacteria were prepared using an ultrasonic homogenizing device. The impact of these bacterial extracts on GMSCs was evaluated through Alizarin Red and Oil Red O staining, cell counting by Trypan Blue staining, and real-time polymerase chain reaction. The findings of our study indicate that the administration of 50 μg/mL L. rhamnosus extract resulted in a greater enhancement of stemness marker expression, osteogenic differentiation, and proliferation of GMSCs compared with an equivalent concentration of L. reuteri extract. Neither of these bacterial extracts revealed any effect on the differentiation of the GMSCs into the adipogenic lineage. These findings suggest that L. rhamnosus extract could be more effective at promoting GMSCs' efficacy in tissue engineering and regenerative medicine.
Collapse
Affiliation(s)
- Ensiyeh Kord-Parijaee
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
- Biomedical and Microbial Advanced Technologies (BMAT) Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Elaheh Ferdosi-Shahandashti
- Biomedical and Microbial Advanced Technologies (BMAT) Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Behnaz Bakhshandeh
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Abazar Pournajaf
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| |
Collapse
|
|
5
|
Karimi F, Montazeri-Najafabady N, Mohammadi F, Azadi A, Koohpeyma F, Gholami A. A potential therapeutic strategy of an innovative probiotic formulation toward topical treatment of diabetic ulcer: an in vivo study. Nutr Diabetes 2024; 14:66. [PMID: 39164243 PMCID: PMC11335896 DOI: 10.1038/s41387-024-00320-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND The 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. Given that the conventional treatments of DUs have failed to prevent later complications completely, developing alternative therapies seems to be crucial. METHODS We designed the stable oleogel-based formulation of viable probiotic cells, including Lactobacillus rhamnosus (L. rhamnosus), Lactobacillus casei (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. Furthermore, the antibiofilm activity of probiotic bacteria was assessed against some common pathogens. RESULTS The 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. 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. rhamnosus showed a significant biofilm inhibition activity against tested pathogens. CONCLUSIONS This experiment demonstrated that the designed formulations containing probiotics, particularly L. acidophilus and L. rhamnosus, play a central role in manipulating diabetic wound healing. It could be suggested as an encouraging nominee for diabetic wound-healing alternative approaches, though further studies in detailed clinical trials are needed.
Collapse
Affiliation(s)
- Farkhonde Karimi
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
| | - Nima Montazeri-Najafabady
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Mohammadi
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Azadi
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farhad Koohpeyma
- Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Gholami
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran.
| |
Collapse
|
|
6
|
Maslova E, EisaianKhongi L, Rigole P, Coenye T, McCarthy RR. Carbon source competition within the wound microenvironment can significantly influence infection progression. NPJ Biofilms Microbiomes 2024; 10:52. [PMID: 38918415 PMCID: PMC11199515 DOI: 10.1038/s41522-024-00518-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 05/08/2024] [Indexed: 06/27/2024] Open
Abstract
It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.
Collapse
Affiliation(s)
- Evgenia Maslova
- Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK
| | - Lara EisaianKhongi
- Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK
| | - Petra Rigole
- Laboratory of Pharmaceutical Microbiology, Ghent University, 9000, Ghent, Belgium
| | - Tom Coenye
- Laboratory of Pharmaceutical Microbiology, Ghent University, 9000, Ghent, Belgium
| | - Ronan R McCarthy
- Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK.
| |
Collapse
|
|
7
|
de Souza T, Monteiro JDC, Curioni CC, Cople-Rodrigues C, Citelli M. Nutrients with Antioxidant Properties and Their Effects on Lower-Limb Ulcers: A Systematic Review. INT J LOW EXTR WOUND 2024; 23:217-230. [PMID: 35072533 DOI: 10.1177/15347346221074861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Chronic lower-limb ulcers (LLUs) are ulcers that fail to proceed through an orderly and timely process to produce anatomic and functional integrity. LLUs reduce the quality of life of affected individuals and are a public health problem. The treatment options include medications or surgery. Nutrition therapy is an important adjunct to improve the clinical picture and healing of LLUs. Considering that nutrients with antioxidant properties can improve the process of tissue healing, this systematic review aimed to evaluate the efficacy of antioxidant nutrient supplementation in the treatment of LLUs through randomized clinical trials. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Cochrane Handbook for Systematic Reviews of Interventions. The guiding question was-can antioxidant nutrients help in the treatment of chronic LLUs? In total, 1184 articles were found when searching for antioxidant nutrients associated with the most common causes of LLUs. Fourteen articles were included in this review after removing duplicates, studies with topical and/or venous use of antioxidants, and articles published in other languages, except English. Omega-3 fatty acids, magnesium, zinc, vitamins A, C, D, and resveratrol along with probiotics positively improved the ulcer healing. These effects were more significant when there was initially a deficiency of the respective supplemented nutrients. Therefore, correcting and maintaining an adequate nutritional status can improve ulcer healing and contribute to the clinical treatment of patients with LLUs.
Collapse
Affiliation(s)
- Thamiris de Souza
- Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | | | | | | | - Marta Citelli
- Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil
| |
Collapse
|
|
8
|
Bădăluță VA, Curuțiu C, Dițu LM, Holban AM, Lazăr V. Probiotics in Wound Healing. Int J Mol Sci 2024; 25:5723. [PMID: 38891909 PMCID: PMC11171735 DOI: 10.3390/ijms25115723] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/20/2024] [Accepted: 05/21/2024] [Indexed: 06/21/2024] Open
Abstract
Wound infections caused by opportunistic bacteria promote persistent infection and represent the main cause of delayed healing. Probiotics are acknowledged for their beneficial effects on the human body and could be utilized in the management of various diseases. They also possess the capacity to accelerate wound healing, due to their remarkable anti-pathogenic, antibiofilm, and immunomodulatory effects. Oral and topical probiotic formulations have shown promising openings in the field of dermatology, and there are various in vitro and in vivo models focusing on their healing mechanisms. Wound dressings embedded with prebiotics and probiotics are now prime candidates for designing wound healing therapeutic approaches to combat infections and to promote the healing process. The aim of this review is to conduct an extensive scientific literature review regarding the efficacy of oral and topical probiotics in wound management, as well as the potential of wound dressing embedding pre- and probiotics in stimulating the wound healing process.
Collapse
Affiliation(s)
- Valentina Alexandra Bădăluță
- Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania; (V.A.B.); (C.C.); (L.M.D.); (V.L.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| | - Carmen Curuțiu
- Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania; (V.A.B.); (C.C.); (L.M.D.); (V.L.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| | - Lia Mara Dițu
- Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania; (V.A.B.); (C.C.); (L.M.D.); (V.L.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| | - Alina Maria Holban
- Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania; (V.A.B.); (C.C.); (L.M.D.); (V.L.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| | - Veronica Lazăr
- Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania; (V.A.B.); (C.C.); (L.M.D.); (V.L.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| |
Collapse
|
|
9
|
Chen WT, Wang XX, Zheng WL, Zhang WQ, Mao LJ, Zhuo JN, Zhou ST, Yang RH. [Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2024; 40:333-341. [PMID: 38664027 DOI: 10.3760/cma.j.cn501225-20231129-00215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 05/01/2024]
Abstract
Objective: To investigate the causality between intestinal flora and hypertrophic scars (HS) of human. Methods: This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora (n=18 473) and HS (n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results: A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions: There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.
Collapse
Affiliation(s)
- W T Chen
- The First Clinical College of Medicine, Guangdong Medical University, Zhanjiang 524023, China
| | - X X Wang
- Department of Burn Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510030, China
| | - W L Zheng
- Department of Burn and Plastic Surgery, the First People's Hospital of Shaoguan, Shaoguan 512000, China
| | - W Q Zhang
- The First Clinical College of Medicine, Guangdong Medical University, Zhanjiang 524023, China
| | - L J Mao
- Department of Burn Plastic Surgery and Wound Repair, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - J N Zhuo
- The First Clinical College of Medicine, Guangdong Medical University, Zhanjiang 524023, China
| | - S T Zhou
- Dermatology Department, Foshan First People's Hospital, Foshan 528000, China
| | - R H Yang
- The First Clinical College of Medicine, Guangdong Medical University, Zhanjiang 524023, China Department of Burn Plastic Surgery and Wound Repair, Guangzhou First People's Hospital, Guangzhou 510180, China
| |
Collapse
|
|
10
|
Alagiakrishnan K, Morgadinho J, Halverson T. Approach to the diagnosis and management of dysbiosis. Front Nutr 2024; 11:1330903. [PMID: 38706561 PMCID: PMC11069313 DOI: 10.3389/fnut.2024.1330903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/12/2024] [Indexed: 05/07/2024] Open
Abstract
All microorganisms like bacteria, viruses and fungi that reside within a host environment are considered a microbiome. The number of bacteria almost equal that of human cells, however, the genome of these bacteria may be almost 100 times larger than the human genome. Every aspect of the physiology and health can be influenced by the microbiome living in various parts of our body. Any imbalance in the microbiome composition or function is seen as dysbiosis. Different types of dysbiosis are seen and the corresponding symptoms depend on the site of microbial imbalance. The contribution of the intestinal and extra-intestinal microbiota to influence systemic activities is through interplay between different axes. Whole body dysbiosis is a complex process involving gut microbiome and non-gut related microbiome. It is still at the stage of infancy and has not yet been fully understood. Dysbiosis can be influenced by genetic factors, lifestyle habits, diet including ultra-processed foods and food additives, as well as medications. Dysbiosis has been associated with many systemic diseases and cannot be diagnosed through standard blood tests or investigations. Microbiota derived metabolites can be analyzed and can be useful in the management of dysbiosis. Whole body dysbiosis can be addressed by altering lifestyle factors, proper diet and microbial modulation. The effect of these interventions in humans depends on the beneficial microbiome alteration mostly based on animal studies with evolving evidence from human studies. There is tremendous potential for the human microbiome in the diagnosis, treatment, and prognosis of diseases, as well as, for the monitoring of health and disease in humans. Whole body system-based approach to the diagnosis of dysbiosis is better than a pure taxonomic approach. Whole body dysbiosis could be a new therapeutic target in the management of various health conditions.
Collapse
Affiliation(s)
| | - Joao Morgadinho
- Kaye Edmonton Clinic, Alberta Health Services, Edmonton, AB, Canada
| | - Tyler Halverson
- Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
| |
Collapse
|
|
11
|
Abdi A, Oroojzadeh P, Valivand N, Sambrani R, Lotfi H. Immunological aspects of probiotics for improving skin diseases: Influence on the Gut-Brain-Skin Axis. Biochem Biophys Res Commun 2024; 702:149632. [PMID: 38340656 DOI: 10.1016/j.bbrc.2024.149632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 01/27/2024] [Accepted: 02/04/2024] [Indexed: 02/12/2024]
Abstract
The interplay between gut microbiota and human health, both mental and physical, is well-documented. This connection extends to the gut-brain-skin axis, linking gut microbiota to skin health. Recent studies have underscored the potential of probiotics and prebiotics to modulate gut microbiota, supported by in vivo and clinical investigations. In this comprehensive review, we explore the immunological implications of probiotics in influencing the gut-skin axis for the treatment and prevention of skin conditions, including psoriasis, acne, diabetic ulcers, atopic dermatitis, and skin cancer. Our analysis reveals that probiotics exert their effects by modulating cytokine production, whether administered orally or topically. Probiotics bolster skin defenses through the production of antimicrobial peptides and the induction of keratinocyte differentiation and regeneration. Yet, many questions surrounding probiotics remain unanswered, necessitating further exploration of their mechanisms of action in the context of skin diseases.
Collapse
Affiliation(s)
- Ali Abdi
- Medical Immunology, Aziz Sancar Institute of Experimental Medicine, İstanbul University, Istanbul, Turkey
| | - Parvin Oroojzadeh
- Student Research Committee, Department of Food Science and Technology, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nassim Valivand
- Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Roshanak Sambrani
- Clinical Research Development Unit of Razi Educational and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hajie Lotfi
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
| |
Collapse
|
|
12
|
Sechovcová H, Mahayri TM, Mrázek J, Jarošíková R, Husáková J, Wosková V, Fejfarová V. Gut microbiota in relationship to diabetes mellitus and its late complications with a focus on diabetic foot syndrome: A review. Folia Microbiol (Praha) 2024; 69:259-282. [PMID: 38095802 DOI: 10.1007/s12223-023-01119-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/05/2023] [Indexed: 04/11/2024]
Abstract
Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.
Collapse
Affiliation(s)
- Hana Sechovcová
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, CAS, Vídeňská, 1083, 142 20, Prague, Czech Republic
- Faculty of Agrobiology, Food and Natural Resources, Department of Microbiology, Nutrition and Dietetics, Czech University of Life Sciences, Prague, Czech Republic
| | - Tiziana Maria Mahayri
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, CAS, Vídeňská, 1083, 142 20, Prague, Czech Republic.
- Department of Veterinary Medicine, University of Sassari, 07100, Sassari, Italy.
| | - Jakub Mrázek
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, CAS, Vídeňská, 1083, 142 20, Prague, Czech Republic
| | - Radka Jarošíková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jitka Husáková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Veronika Wosková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Vladimíra Fejfarová
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Second Faculty of Medicine, Charles University, Prague, Czech Republic
| |
Collapse
|
|
13
|
Zielińska M, Pawłowska A, Orzeł A, Sulej L, Muzyka-Placzyńska K, Baran A, Filipecka-Tyczka D, Pawłowska P, Nowińska A, Bogusławska J, Scholz A. Wound Microbiota and Its Impact on Wound Healing. Int J Mol Sci 2023; 24:17318. [PMID: 38139146 PMCID: PMC10743523 DOI: 10.3390/ijms242417318] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/04/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
Wound healing is a complex process influenced by age, systemic conditions, and local factors. The wound microbiota's crucial role in this process is gaining recognition. This concise review outlines wound microbiota impacts on healing, emphasizing distinct phases like hemostasis, inflammation, and cell proliferation. Inflammatory responses, orchestrated by growth factors and cytokines, recruit neutrophils and monocytes to eliminate pathogens and debris. Notably, microbiota alterations relate to changes in wound healing dynamics. Commensal bacteria influence immune responses, keratinocyte growth, and blood vessel development. For instance, Staphylococcus epidermidis aids keratinocyte progression, while Staphylococcus aureus colonization impedes healing. Other bacteria like Group A Streptococcus spp. And Pseudomonas affect wound healing as well. Clinical applications of microbiota-based wound care are promising, with probiotics and specific bacteria like Acinetobacter baumannii aiding tissue repair through molecule secretion. Understanding microbiota influence on wound healing offers therapeutic avenues. Tailored approaches, including probiotics, prebiotics, and antibiotics, can manipulate the microbiota to enhance immune modulation, tissue repair, and inflammation control. Despite progress, critical questions linger. Determining the ideal microbiota composition for optimal wound healing, elucidating precise influence mechanisms, devising effective manipulation strategies, and comprehending the intricate interplay between the microbiota, host, and other factors require further exploration.
Collapse
Affiliation(s)
- Małgorzata Zielińska
- Ist Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland; (M.Z.); (A.O.)
| | - Agnieszka Pawłowska
- Students Research Group of Obstetrics and Gynecology Department at St. Sophia Hospital, 01-004 Warsaw, Poland; (A.P.)
| | - Anna Orzeł
- Ist Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland; (M.Z.); (A.O.)
| | - Luiza Sulej
- Students Research Group of Obstetrics and Gynecology Department at St. Sophia Hospital, 01-004 Warsaw, Poland; (A.P.)
| | - Katarzyna Muzyka-Placzyńska
- Ist Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland; (M.Z.); (A.O.)
| | - Arkadiusz Baran
- Ist Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland; (M.Z.); (A.O.)
| | - Dagmara Filipecka-Tyczka
- Ist Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland; (M.Z.); (A.O.)
| | - Paulina Pawłowska
- Students Scientific Association, Department of Hygiene and Epidemiology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Aleksandra Nowińska
- Students Scientific Association, Department of Hygiene and Epidemiology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Joanna Bogusławska
- Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland;
| | - Anna Scholz
- Ist Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland; (M.Z.); (A.O.)
| |
Collapse
|
|
14
|
Müge Karakayalı E, Kocamaz E, Alpay Ş, Önal T, Öztatlici M, Duruşma R, Ozel HF, Mete M, Barutcuoglu M, Kutlu N, Tuğlu Mİ. Histological and electroencephalographic demonstration of probiotic effect for reduce of oxidative stress and apoptosis in experimental traumatic brain injury. ULUS TRAVMA ACIL CER 2023; 29:1203-1211. [PMID: 37889022 PMCID: PMC10771235 DOI: 10.14744/tjtes.2023.80743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 07/26/2023] [Accepted: 10/07/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND The gut microbiota modulates nervous system function. In the literature, it has been shown that this modula-tion is used in many nervous system injuries through oxidative stress (OS) and apoptosis mechanisms. In this study, it was aimed to investigate the neuroprotective effects of probiotic (PB) treatment in a rat traumatic brain injury (TBI) model with histological and electroencephalographic (EEG) data. METHODS Forty male Wistar albino rats were divided into four groups. Group 1 was the control group (CONTROL, n=10) and no trauma was applied. Group 2 was the trauma group with the weight-drop technique (TBH, n=10). Group 3 was the sham group (SHAM), (TBH+sterile saline [SS], n=10) rats were given 500 µL of SS per day by oral gavage. Group 4 was the PB treatment group, (TBH+PB, n=10) rats were treated daily for 7 days with 500 µL of PB oral gavage. Brain samples were collected 7 days after trauma. Histopathological evaluation of brain samples was done with HE. OS with Endothelial nitric oxide synthase, vascularization with Vas-cular Endothelial Growth Factor, gliosis with S100, and apoptosis with caspase 3 were evaluated immunohistochemically. Apoptotic index was determined with TUNEL. In addition, EEG and somatosensory evoked potential (SEP) recording findings were compared. RESULTS It was determined by HE staining that there was a significant (P<0.001) damage in the TBI and sham groups compared to the control group. It was found that PB treatment provided a significant (P<0.01) improvement in the damage created. While OS (P<0.01), gliosis (P<0.01), and apoptosis (P<0.05) decreased with PB treatment, angiogenesis (P<0.01) increased. In support of these findings, in the software-mediated EEG and SUP examination; Delta wave power and theta/alpha ratio increased with TBI and de-creased with PB treatment. CONCLUSION The results showed that PB treatment provided a significant improvement in rats by reducing OS, apoptosis, and gliosis and increasing vascularity. To the best of our knowledge in the literature, it was shown for the 1st time that histological results for the treatment of PB were supported by software-mediated EEG and SEP analysis.
Collapse
Affiliation(s)
- Emine Müge Karakayalı
- Department of Medical Microbiology, Izmir Democracy University Faculty of Medicine, İzmir-Türkiye
| | - Erdoğan Kocamaz
- Department of Histology and Embryology, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| | - Şüheda Alpay
- Department of Physiology Department, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| | - Tuna Önal
- Department of Histology and Embryology, Bandırma Onyedi Eylül,University Faculty of Medicine, Bandırma-Türkiye
| | - Mustafa Öztatlici
- Department of Histology and Embryology, Gaziantep Islam Bilim ve Teknoloji University Faculty of Medicine, Gaziantep-Türkiye
| | - Rabia Duruşma
- Department of Histology and Embryology, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| | - Hasan Fehmi Ozel
- Department of Health Sciences, Celal Bayar University School of Vocation, Manisa-Türkiye
| | - Mesut Mete
- Department of Neurosurgery, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| | - Mustafa Barutcuoglu
- Department of Neurosurgery, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| | - Necip Kutlu
- Department of Physiology Department, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| | - Mehmet İbrahim Tuğlu
- Department of Histology and Embryology, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye
| |
Collapse
|
|
15
|
Abstract
A wound is an injury to the skin or damage to the body tissue. The healing process differs between various kinds of wounds. Treatment of hard-to-heal (chronic) wounds becomes challenging for healthcare practitioners, especially if patients have underlying health complications such as diabetes. Infection of wounds is another factor that interferes with the healing process and extends its duration. Active research is being conducted into the development of advanced wound dressing technologies. These wound dressings are intended to manage the exudate, reduce bacterial infection and speed up the healing process. Probiotics have been receiving much attention because of their potential application in the clinical field, especially in diagnostics and treatment strategies of various infectious and non-infectious diseases. The host immune-modulatory response and antimicrobial activity of probiotics are expanding their role in the development of improved wound dressing technology.
Collapse
Affiliation(s)
- Shanmugaraja Meenakshi
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam-603103, Chennai, Tamil Nadu, India
| | - Ramadevi Santhanakumar
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam-603103, Chennai, Tamil Nadu, India
| |
Collapse
|
|
16
|
Michels M, Córneo E, Rocha LBG, Dias R, Voytena APL, Rossetto M, Ramlov F, Dal-Pizzol F, Jesus GFA. Paraprobiotics strains accelerate wound repair by stimulating re-epithelialization of NIH-3T3 cells, decreasing inflammatory response and oxidative stress. Arch Microbiol 2023; 205:134. [PMID: 36959516 DOI: 10.1007/s00203-023-03469-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 03/06/2023] [Indexed: 03/25/2023]
Abstract
The present study aimed to evaluate the potential and specificity of the inflammatory and antioxidant response of Microbe-Associated Molecular Patterns (MAMPs) in NIH-3T3 fibroblast cells, as well as in the healing process of skin wounds. Cells (NIH-3T3) were cultivated in supplemented specific medium. NIH-3T3 cells were treated with MAMPs (Bifidobacterium lactis or Lactobacillus casei or Lactobacillus gasseri or Lactobacillus paracasei or Streptococcus thermophilus), at two concentrations and insulted with LPS or H2O2. Cell viability, myeloperoxidase activity, nitrite/nitrate, oxidative damage and inflammatory parameters were measured. In addition, scratch assay was performed. Significant scratch closure was observed after 24 h and 48 h, and the effect of 0.1 g/mL MAMPs on wound healing was found to be highly statistically significant. In the viability cellular assay, Lactobacillus showed better response in 0.1 g/mL dose, whereas B. lactis and S. thermophilus showed better response in 0.01 g/mL dose. There was reduction in IL-6 and IL-1β levels in all treatments insulted with LPS. MAMP's showed preventive efficacy in reducing the effects caused by LPS. The MAMP's action in decreasing the production of ROS, inflammatory activity and increasing cell viability, besides significant cell proliferation during wound healing processes suggests remodeling mechanisms and new possibilities for wound healing.
Collapse
Affiliation(s)
- Monique Michels
- Gabbia Biotechnology, Barra Velha, Santa Catarina, Brazil.
- Biohall Research and Innovation, Itajaí, Santa Catarina, Brazil.
| | - Emily Córneo
- Laboratory of Experimental Pathophysiology-Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Luana Bezerra Gonçalves Rocha
- Laboratory of Experimental Pathophysiology-Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Rodrigo Dias
- Laboratory of Experimental Pathophysiology-Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | | | | | | | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology-Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Gabriel Fernandes Alves Jesus
- Gabbia Biotechnology, Barra Velha, Santa Catarina, Brazil
- Biohall Research and Innovation, Itajaí, Santa Catarina, Brazil
| |
Collapse
|
|
17
|
Wang G, Lin Z, Li Y, Chen L, Reddy SK, Hu Z, Garza LA. Colonizing microbiota is associated with clinical outcomes in diabetic wound healing. Adv Drug Deliv Rev 2023; 194:114727. [PMID: 36758858 PMCID: PMC10163681 DOI: 10.1016/j.addr.2023.114727] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 02/02/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023]
Abstract
With the development of society and the improvement of life quality, more than 500 million people are affected by diabetes. More than 10 % of people with diabetes will suffer from diabetic wounds, and 80 % of diabetic wounds will reoccur, so the development of new diabetic wound treatments is of great importance. The development of skin microbe research technology has gradually drawn people's attention to the complex relationship between microbes and diabetic wounds. Many studies have shown that skin microbes are associated with the outcome of diabetic wounds and can even be used as one of the indicators of wound prognosis. Skin microbes have also been found to have the potential to treat diabetic wounds. The wound colonization of different bacteria can exert opposing therapeutic effects. It is necessary to fully understand the skin microbes in diabetic wounds, which can provide valuable guidance for clinical diabetic wound treatment.
Collapse
Affiliation(s)
- Gaofeng Wang
- Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510515, China; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21210, USA.
| | - Zhen Lin
- Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510515, China
| | - Yue Li
- Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510515, China
| | - Lu Chen
- Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510515, China
| | - Sashank K Reddy
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21210, USA; Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
| | - Zhiqi Hu
- Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510515, China
| | - L A Garza
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21210, USA; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21210, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21210, USA.
| |
Collapse
|
|
18
|
Awasthi A, Corrie L, Vishwas S, Gulati M, Kumar B, Chellappan DK, Gupta G, Eri RD, Dua K, Singh SK. Gut Dysbiosis and Diabetic Foot Ulcer: Role of Probiotics. Pharmaceutics 2022; 14:pharmaceutics14112543. [PMID: 36432734 PMCID: PMC9699533 DOI: 10.3390/pharmaceutics14112543] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/07/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022] Open
Abstract
Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. Hence, to manage DFU/DWs, various attempts have been made, including treating wounds systematically/topically using synthetic drugs, herbal drugs, or tissue engineering based surgical dressings. However, less attention has been paid to the intrinsic factors that are also the leading cause of diabetes mellitus (DM) and its complications. One such factor is gut dysbiosis, which is one of the major causes of enhancing the counts of Gram-negative bacteria. These bacteria produce lipopolysaccharides, which are a major contributing factor toward insulin resistance and inflammation due to the generation of oxidative stress and immunopathy. These all lead to DM and DFU. Probiotics are the commercial form of beneficial gut microbes that are taken as nutraceuticals by people of all ages to improve gut immunity and prevent gut dysbiosis. However, the role of probiotics has been less explored in the management of DFU. Hence, the therapeutic potential of probiotics in managing DFU is fully described in the current review. This report covers the linkage between gut dysbiosis and DFU, sources of probiotics, the mechanisms of probiotics in DW healing, and the impact of probiotic supplementation in treating DFU. In addition, techniques for the stabilization of probiotics, market status, and patents related to probiotics have been also covered. The relevant data were gathered from PubMed, Scopus, Taylor and Francis, Science Direct, and Google Scholar. Our systematic review discusses the utilization of probiotic supplementation as a nutraceutical for the management of DFU.
Collapse
Affiliation(s)
- Ankit Awasthi
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Leander Corrie
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Sukriti Vishwas
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Bimlesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jaipur 302017, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 602105, India
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, India
| | - Rajaraman D. Eri
- School of Health Sciences, The University of Tasmania, Launceston, TAS 7248, Australia
- Correspondence: (R.D.E.); or (S.K.S.); Tel.: +61-363245467 (R.D.E.); +91-9888720835 (S.K.S.)
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Correspondence: (R.D.E.); or (S.K.S.); Tel.: +61-363245467 (R.D.E.); +91-9888720835 (S.K.S.)
| |
Collapse
|
|
19
|
Da Porto A, Miranda C, Brosolo G, Zanette G, Michelli A, Ros RD. Nutritional supplementation on wound healing in diabetic foot: What is known and what is new? World J Diabetes 2022; 13:940-948. [PMID: 36437863 PMCID: PMC9693742 DOI: 10.4239/wjd.v13.i11.940] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/13/2022] [Accepted: 10/11/2022] [Indexed: 11/11/2022] Open
Abstract
Non-healing diabetic foot ulcers (DFU) are the most notable and striking complications of diabetes mellitus. More than 25% of nonhealing DFU can ultimately lead to amputation of the lower extremity within 6-18 mo after the first manifestation of the wound. Although wound healing is complex, nutritional status is crucial in soft tissue repair. Malnutrition is highly prevalent and overlooked in patients with diabetes and chronic wounds. Moreover, to date, we do not have clear recommendations or evidence about the use of nutritional supplements for improving wound healing in patients with DFU. In this article the authors briefly analyzed the current evidence on the use of nutritional supplements of proteins or amino acids, fatty acids, probiotics, vitamins, and trace elements in the wound healing process in patients with DFU.
Collapse
Affiliation(s)
- Andrea Da Porto
- Department on Internal Medicine, University of Udine, Udine 33100, Italy
| | - Cesare Miranda
- Department of Internal Medicine, Clinic of Endocrinology and Metabolism Diseases Azienda Sanitaria Friuli Occidentale, Pordenone 33170, Italy
| | - Gabriele Brosolo
- Department on Internal Medicine, University of Udine, Udine 33100, Italy
| | - Giorgio Zanette
- Department of Internal Medicine, Clinic of Endocrinology and Metabolism Diseases Azienda Sanitaria Friuli Occidentale, Pordenone 33170, Italy
| | - Andrea Michelli
- Department of Internal Medicine , SC Diabete e Centro Trattamento Piede Diabetico, Monfalcone 34074, Gorizia, Italy
| | - Roberto Da Ros
- Department of Internal Medicine , SC Diabete e Centro Trattamento Piede Diabetico, Monfalcone 34074, Gorizia, Italy
| |
Collapse
|
|
20
|
Srivastava P, Sondak T, Sivashanmugam K, Kim KS. A Review of Immunomodulatory Reprogramming by Probiotics in Combating Chronic and Acute Diabetic Foot Ulcers (DFUs). Pharmaceutics 2022; 14:2436. [PMID: 36365254 PMCID: PMC9699442 DOI: 10.3390/pharmaceutics14112436] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/02/2022] [Accepted: 11/08/2022] [Indexed: 08/29/2023] Open
Abstract
Diabetic foot ulcers (DFUs) are characterized by a lack of angiogenesis and distal limb diabetic neuropathy. This makes it possible for opportunistic pathogens to protect the biofilm-encased micro-communities, causing a delay in wound healing. The acute and chronic phases of DFU-associated infections are distinguished by the differential expression of innate proinflammatory cytokines and tumor necrosis factors (TNF-α and -β). Efforts are being made to reduce the microbial bioburden of wounds by using therapies such as debridement, hyperbaric oxygen therapy, shock wave therapy, and empirical antibiotic treatment. However, the constant evolution of pathogens limits the effectiveness of these therapies. In the wound-healing process, continuous homeostasis and remodeling processes by commensal microbes undoubtedly provide a protective barrier against diverse pathogens. Among commensal microbes, probiotics are beneficial microbes that should be administered orally or topically to regulate gut-skin interaction and to activate inflammation and proinflammatory cytokine production. The goal of this review is to bridge the gap between the role of probiotics in managing the innate immune response and the function of proinflammatory mediators in diabetic wound healing. We also highlight probiotic encapsulation or nanoformulations with prebiotics and extracellular vesicles (EVs) as innovative ways to tackle target DFUs.
Collapse
Affiliation(s)
- Prakhar Srivastava
- Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University, Busan 46241, Korea
| | - Tesalonika Sondak
- Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University, Busan 46241, Korea
| | - Karthikeyan Sivashanmugam
- School of Biosciences and Technology, High Throughput Screening Lab, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Kwang-sun Kim
- Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University, Busan 46241, Korea
| |
Collapse
|
|
21
|
Patel BK, Patel KH, Huang RY, Lee CN, Moochhala SM. The Gut-Skin Microbiota Axis and Its Role in Diabetic Wound Healing-A Review Based on Current Literature. Int J Mol Sci 2022; 23:ijms23042375. [PMID: 35216488 PMCID: PMC8880500 DOI: 10.3390/ijms23042375] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/15/2022] [Accepted: 02/17/2022] [Indexed: 12/18/2022] Open
Abstract
Diabetic foot ulcers (DFU) are a growing concern worldwide as they pose complications in routine clinical practices such as diagnosis and management. Bacterial interactions on the skin surface are vital to the pathophysiology of DFU and may control delayed wound healing. The microbiota from our skin directly regulates cutaneous health and disease by interacting with the numerous cells involved in the wound healing mechanism. Commensal microbiota, in particular, interact with wound-repairing skin cells to enhance barrier regeneration. The observed microbes in DFU include Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, and several anaerobes. Skin commensal microbes, namely S. epidermidis, can regulate the gamma delta T cells and induce Perforin-2 expression. The increased expression of Perforin-2 by skin cells destroyed S. aureus within the cells, facilitating wound healing. Possible crosstalk between the human commensal microbiome and different cell types involved in cutaneous wound healing promotes the immune response and helps to maintain the barrier function in humans. Wound healing is a highly well-coordinated, complex mechanism; it can be devastating if interrupted. Skin microbiomes are being studied in relation to the gut-skin axis along with their effects on dermatologic conditions. The gut-skin axis illustrates the connection wherein the gut can impact skin health due to its immunological and metabolic properties. The precise mechanism underlying gut-skin microbial interactions is still unidentified, but the immune and endocrine systems are likely to be involved. Next-generation sequencing and the development of bioinformatics pipelines may considerably improve the understanding of the microbiome-skin axis involved in diabetic wound healing in a much more sophisticated way. We endeavor to shed light on the importance of these pathways in the pathomechanisms of the most prevalent inflammatory conditions including the diabetes wound healing, as well as how probiotics may intervene in the gut-skin axis.
Collapse
Affiliation(s)
- Bharati Kadamb Patel
- Department of Surgery, National University of Singapore, Singapore 119228, Singapore; (B.K.P.); (C.N.L.)
| | | | - Ryan Yuki Huang
- Canyon Crest Academy, San Diego, CA 92130, USA;
- Department of Mechanical and Aerospace Engineering, University of California, San Diego, CA 92093, USA
| | - Chuen Neng Lee
- Department of Surgery, National University of Singapore, Singapore 119228, Singapore; (B.K.P.); (C.N.L.)
| | - Shabbir M. Moochhala
- Department of Surgery, National University of Singapore, Singapore 119228, Singapore; (B.K.P.); (C.N.L.)
- Department of Pharmacology, National University of Singapore, Singapore 117600, Singapore
- Correspondence:
| |
Collapse
|
|
22
|
Gestational Diabetes, Colorectal Cancer, Bariatric Surgery, and Weight Loss among Diabetes Mellitus Patients: A Mini Review of the Interplay of Multispecies Probiotics. Nutrients 2021; 14:nu14010192. [PMID: 35011065 PMCID: PMC8747162 DOI: 10.3390/nu14010192] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 01/15/2023] Open
Abstract
Diabetes mellitus has been steadily increasing over the past decades and is one of the most significant global public health concerns. Diabetes mellitus patients have an increased risk of both surgical and post-surgical complications. The post-surgical risks are associated with the primary condition that led to surgery and the hyperglycaemia per se. Gut microbiota seems to contribute to glucose homeostasis and insulin resistance. It affects the metabolism through body weight and energy homeostasis, integrating the peripheral and central food intake regulatory signals. Homeostasis of gut microbiota seems to be enhanced by probiotics pre and postoperatively. The term probiotics is used to describe some species of live microorganisms that, when administered in adequate amounts, confer health benefits on the host. The role of probiotics in intestinal or microbial skin balance after abdominal or soft tissue elective surgeries on DM patients seems beneficial, as it promotes anti-inflammatory cytokine production while increasing the wound-healing process. This review article aims to present the interrelation of probiotic supplements with DM patients undergoing elective surgeries.
Collapse
|
|
23
|
Santos MMR, Cavalcante ACFPS, Amaral LAD, Souza GHOD, Santos BSD, Portugal LC, Bittencourt Junior FF, Troquez T, Rafacho BPM, Hiane PA, Santos EFD. Combination of cafeteria diet with intraperitoneally streptozotocin in rats. A type-2 diabetes model. Acta Cir Bras 2021; 36:e360702. [PMID: 34431921 PMCID: PMC8405242 DOI: 10.1590/acb360702] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 06/08/2021] [Indexed: 11/22/2022] Open
Abstract
Purpose To develop a model of induction of type-2 diabetes (DM2) by combining low
doses of streptozotocin (STZ) and a cafeteria diet. Methods Forty male Wistar rats (200 g) were allocated into four groups: control
(non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg
(diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with
a single intraperitoneal injection of STZ after four weeks of cafeteria diet
in the three diabetic groups. All animals were evaluated as for
anthropometric, and biochemical analyses, as well as liver, kidney and
pancreas histological analyses. Results Lower weight gain, higher water intake, higher Lee index, hyperglycemia and
modified total protein, urea, alpha-amylase, as well as insulin resistance,
hepatic steatosis, pancreas, and kidney injury were observed in animals
treated with 35 and 40 mg/kg of STZ. Conclusions The results show that the experimental model using cafeteria diet associated
with 35 mg/kg of STZ is a low-cost model and efficient in order to develop
DM2, confirmed by the presence of polydipsia, hyperglycemia, altered
biochemical tests, insulin resistance and damages to the liver, pancreas and
kidney, which is similar to the disease found in humans.
Collapse
|
|
24
|
Costa ACD, Santa-Cruz F, Ferraz ÁAB. WHAT'S NEW IN INFECTION ON SURGICAL SITE AND ANTIBIOTICOPROPHYLAXIS IN SURGERY? ACTA ACUST UNITED AC 2021; 33:e1558. [PMID: 33503118 PMCID: PMC7836071 DOI: 10.1590/0102-672020200004e1558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/11/2020] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Infection of the surgical site is the common complication, with significant rates of morbidity and mortality, representing a considerable economic problem for the health system. OBJECTIVE To carry out a narrative review of the literature on surgical site infection and the principles of antibiotic prophylaxis to update the knowledge of its use in surgery. METHOD Medline, Ovid, Google Scholar, National Library of Medicine (PubMed), Cochrane and SciELO were used for the research. The keywords used were "anti-bacterial agents"; "antibioticoprophylaxis" AND "surgical wound infection". The inclusion criteria were articles of recent publication, with full texts available and performed in humans. RESULT A total of 29 articles were evaluated and selected according to the eligibility criteria. CONCLUSION Infection of the surgical site is the most common postoperative complication. The key point of its prevention is the combination of several interventions that aim to reduce risk factors, such as: compliance with the new guidelines of the Center for Disease Control and Prevention; the principles of the use of prophylactic antibiotics; factors and risk index of the surgical site; administration time; duration and dosage of antibiotics. These data are available in this article.
Collapse
Affiliation(s)
| | | | - Álvaro A B Ferraz
- Department of Surgery, Federal University of Pernambuco, Recife, PE, Brazil
| |
Collapse
|