Probiotics in Wound Healing
Abstract
:1. Introduction
2. Types of Probiotics in Wound Healing
2.1. Oral Probiotics
2.2. Topical Probiotics
3. Mechanisms of Probiotics in Wound Healing
4. Human Studies Supporting the Role of Probiotics in Wound Healing
5. Wound Dressings with Probiotics and Prebiotics
Type of Study | Dressing Type | Probiotics/ Prebiotics | Pathogenic Indicator Microorganisms | Effects/Mode of Action | Intended Application | References |
---|---|---|---|---|---|---|
in vivo (mice model) in vitro | Sponge dressings | L. plantarum UBLP-40 (MTCC 5380) | S. aureus 9144 | Decrease bacterial attachment and growth; Promote tissue granulation. Accelerate wound healing; Decrease in matrix metalloproteases, TNF-α levels. Increase in TGF-β, VEGF, antioxidant enzymes levels. | Improved treatment of chronic infected wounds | Sandhu et al., 2023 [83] |
in vivo (rat model) | Hiybrid bilayer wound dressing | L. brevis (KCTC 3498) | S. aureus subsp. Aureus KCCM 40050 | Growth inhibition in planktonic and biofilm bacterial cultures; Reduction in the number of mast cells, microvessels, granulation tissue area. | Better recovery and treatment of infected wounds | Kim et al., 2022 [78] |
in vivo (rat model) | Probiotic hydrogels | Lacticaseibacillus paracasei (TYM202), extracellular polysaccharides 9EPS0 from B. velezensis (M76T11B) | E. coli, S. aureus | Inhibition of growth and attachment of the pathogenic agents; Reduced inflammation; Stimulated collagen deposition; Promoted angiogenesis. | Improved treatment of skin conditions | Xu et al., 2024 [82] |
in vivo (Wistar rat model) in vitro | Microencapsulated probiotic cells and prebiotics in different types of coatings (pectin, sodium alginate, and chitosan) | Lactiplantibacillus plantarum (ATCC 1058), fructooligosaccharide (FOS) | P. aeruginosa ATCC 9027, S. aureus ATCC 6538 | Accelerate wound healing process by increasing wound closure rate; Inhibition of growth and biofilm formation in the evaluated Gram-negative strains. | Improved treatment of infected burn wound | Farahani et al., 2023 [81] |
6. Conclusions
Funding
Conflicts of Interest
References
- Schultz, G.S.; Chin, G.A.; Moldawer, L.; Diegelmann, R.F. Principles of Wound Healing. In Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists, 1st ed.; Fitridge, R., Thompson, M.M., Eds.; University of Adelaide Press: Adelaide, Australia, 2011; Volume 1, p. 23. Available online: https://www.ncbi.nlm.nih.gov/books/NBK534261/ (accessed on 20 April 2024).
- Peña, O.A.; Martin, P. Cellular and molecular mechanisms of skin wound healing. Nat. Rev. Mol. Cell Biol. 2024, 1–18. [Google Scholar] [CrossRef] [PubMed]
- Wilkinson, H.N.; Hardman, M.J. Wound healing: Cellular mechanisms and pathological outcomes. Open Biol. 2020, 10, 2–8. [Google Scholar] [CrossRef]
- Criollo-Mendoza, M.S.; Contreras-Angulo, L.A.; Leyva-López, N.; Gutiérrez-Grijalva, E.P.; Jiménez-Ortega, L.A.; Heredia, J.B. Wound Healing Properties of Natural Products: Mechanisms of Action. Molecules 2023, 28, 598. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Wang, M.; Wen, Y.; Zhang, H.; Zhao, G.N.; Gao, Q. Signaling pathways in macrophages: Molecular mechanisms and therapeutic targets. MedComm 2020, 4, 2–25. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Alexander, P.B.; Wang, X.F. TGF-β family signaling in the control of cell proliferation and survival. Cold Spring Harb. Perspect. Biol. 2017, 9, 2–16. [Google Scholar] [CrossRef] [PubMed]
- Deng, Z.; Fan, T.; Xiao, C.; Tian, H.; Zheng, Y.; Li, C. TGF-β signaling in health, disease, and therapeutics. Signal Transduct. Target. Ther. 2024, 9, 61. [Google Scholar] [CrossRef] [PubMed]
- Piera-Velazquez, S.; Jimenez, S.A. Endothelial to mesenchymal transition: Role in physiology and in the pathogenesis of human diseases. Physiol. Rev. 2019, 99, 1281–1324. [Google Scholar] [CrossRef] [PubMed]
- Wallace, H.A.; Basehore, B.M.; Zito, P.M. Wound Healing Phases. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: https://www.ncbi.nlm.nih.gov/books/NBK470443/ (accessed on 15 May 2024).
- Tracy, L.E.; Minasian, R.A.; Caterson, E.J. Extracellular matrix and dermal fibroblast function in the healing wound. Adv. Wound Care 2016, 5, 119–136. [Google Scholar] [CrossRef] [PubMed]
- Farooq, M.; Khan, A.W.; Kim, M.S.; Choi, S. The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration. Cells 2021, 10, 3242. [Google Scholar] [CrossRef]
- Shi, X.; Young, C.D.; Zhou, H.; Wang, X. Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts. Biomolecules 2020, 10, 1666. [Google Scholar] [CrossRef]
- Zhu, W.H.; MacIntyre, A.; Nicosia, R.F. Regulation of angiogenesis by vascular endothelial growth factor and angiopoietin-1 in the rat aorta model: Distinct temporal patterns of intracellular signaling correlate with induction of angiogenic sprouting. Am. J. Pathol. 2002, 161, 823–830. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.L.; Chen, H.H.; Zheng, L.L.; Sun, L.P.; Shi, L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct. Target Ther. 2023, 8, 198. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Khalil, R.A. Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease. Adv. Pharmacol. 2018, 81, 241–330. [Google Scholar] [CrossRef] [PubMed]
- Zhou, S.; Xie, M.; Su, J.; Cai, B.; Li, J.; Zhang, K. New insights into balancing wound healing and scarless skin repair. J. Tissue Eng. 2023, 14, 2–20. [Google Scholar] [CrossRef] [PubMed]
- Correa-Gallegos, D.; Rinkevich, Y. Cutting into wound repair. FEBS J. 2022, 289, 5034–5048. [Google Scholar] [CrossRef] [PubMed]
- Shetty, V.; Bertolami, C.N. Wound Healing. In Peterson’s Principles of Oral and Maxillofacial Surgery, 4th ed.; Miloro, M., Ghali, G.E., Larsen, P.E., Waite, P., Eds.; Springer International Publishing: Shelton, CT, USA, 2022; Volume 1, pp. 3–18. [Google Scholar] [CrossRef]
- Ye, J.; Chen, X. Current Promising Strategies against Antibiotic-Resistant Bacterial Infections. Antibiotics 2022, 12, 67. [Google Scholar] [CrossRef] [PubMed]
- Michalczyk, E.R.; Senderak, A.R.; Jones, R.M.; Coulter, W.H.; Goudy, S.L. Changes in the microbiome during oral wound. Dent. Rev. 2022, 2022. 2, 100040. [Google Scholar] [CrossRef]
- Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514. [Google Scholar] [CrossRef] [PubMed]
- Barzegar, H.; Alizadeh Behbahani, B.; Mirzaei, A.; Ghodsi Sheikhjan, M. Assessing the protection mechanisms against Enterobacter aerogenes by analyzing aggregation, adherence, antagonistic activity, and safety properties of potentially probiotic strain Lactobacillus brevis G145. Microb. Pathog. 2023, 181, 106175. [Google Scholar] [CrossRef]
- Masheghati, F.; Asgharzadeh, M.R.; Jafari, A.; Masoudi, N.; Maleki-Kakelar, H. The role of gut microbiota and probiotics in preventing, treating, and boosting the immune system in colorectal cancer. Life Sci. 2024, 344, 122529. [Google Scholar] [CrossRef]
- Fijan, S.; Frauwallner, A.; Langerholc, T.; Krebs, B.; Ter Haar Née Younes, J.A.; Heschl, A.; Mičetić Turk, D.; Rogelj, I. Efficacy of using probiotics with antagonistic activity against pathogens of wound infections: An integrative review of literature. BioMed Res. Int. 2019, 2019, 2–19. [Google Scholar] [CrossRef] [PubMed]
- Gudadappanavar, A.M.; Hombal, P.R.; Timashetti, S.S.; Javali, S.B. Influence of Lactobacillus acidophilus and Lactobacillus plantarum on wound healing in male Wistar rats-an experimental study. Int. J. Appl. Basic Med. Res. 2017, 7, 233. [Google Scholar] [CrossRef]
- Piqué, N.; Berlanga, M.; Miñana-Galbis, D. Health benefits of heat-killed (Tyndallized) probiotics: An overview. Int. J. Mol. Sci. 2019, 20, 2534. [Google Scholar] [CrossRef] [PubMed]
- Maldonado Galdeano, C.; Cazorla, S.I.; Lemme Dumit, J.M.; Vélez, E.; Perdigón, G. Beneficial effects of probiotic consumption on the immune system. Ann. Nutr. Metab. 2019, 74, 115–124. [Google Scholar] [CrossRef] [PubMed]
- Knackstedt, R.; Knackstedt, T.; Gatherwright, J. The role of topical probiotics on wound healing: A review of animal and human studies. Int. Wound J. 2020, 17, 1687–1694. [Google Scholar] [CrossRef] [PubMed]
- Tagliari, E.; Campos, L.F.; Casagrande, T.A.C.; Fuchs, T.; de Noronha, L.; Campos, A.C.L. Effects of oral probiotics administration on the expression of transforming growth factor β and the proinflammatory cytokines interleukin 6, interleukin 17, and tumor necrosis factor α in skin wounds in rats. J. Parenter. Enter. Nutr. 2022, 46, 721–729. [Google Scholar] [CrossRef] [PubMed]
- Ong, J.S.; Taylor, T.D.; Yong, C.C.; Khoo, B.Y.; Sasidharan, S.; Choi, S.B.; Ohno, H.; Liong, M.T. Lactobacillus plantarum USM8613 aids in wound healing and suppresses Staphylococcus aureus infection at wound sites. Probiotics Antimicrob. Proteins 2020, 12, 125–137. [Google Scholar] [CrossRef]
- Marquez, R.; Zwilling, J.; Zambrano, F.; Tolosa, L.; Marquez, M.E.; Venditti, R.; Jameel, H.; Gonzales, R. Nanoparticles and essential oils with antiviral activity on packaging and surfaces: An overview of their selection and application. J. Surfactants Deterg. 2022, 25, 667–701. [Google Scholar] [CrossRef]
- Togo, C.; Zidorio, A.P.; Gonçalves, V.; Botelho, P.; de Carvalho, K.; Dutra, E. Does Probiotic Consumption Enhance Wound Healing? A Systematic Review. Nutrients 2022, 14, 111. [Google Scholar] [CrossRef]
- Abdollahpour, D.; Homayouni-Rad, A.; Nourizadeh, R.; Hakimi, S.; Mehrabi, E. The effect of probiotic supplementation on episiotomy wound healing among primiparous women: A triple-blind randomized clinical trial. BMC Complement Med. Ther. 2023, 23, 149. [Google Scholar] [CrossRef]
- Wälivaara, D.Å.; Sjögren, I.; Gerasimcik, N.; Yucel-Lindberg, T.; Twetman, S.; Abrahamsson, P. Effects of Lactobacillus reuteri-containing lozenges on healing after surgical removal of mandibular third molars: A randomised controlled trial. Benef. Microbes 2019, 10, 653–659. [Google Scholar] [CrossRef]
- Mohseni, S.; Bayani, M.; Bahmani, F.; Tajabadi-Ebrahimi, M.; Bayani, M.A.; Jafari, P.; Asemi, Z. The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Diabetes/Metab. Res. Rev. 2018, 34, e2970. [Google Scholar] [CrossRef]
- Esposito, C.; Roberti, A.; Turrà, F.; Cerulo, M.; Severino, G.; Settimi, A.; Escolino, M. Frequency of antibiotic-associated diarrhea and related complications in pediatric patients who underwent hypospadias repair: A comparative study using probiotics vs placebo. Probiotics Antimicrob. Proteins 2018, 10, 323–328. [Google Scholar] [CrossRef]
- Putra, O.; Pebrianton, H.; Suharjono, S.; Iswinarno, I.; Rahayu, D. The Role of Probiotics in Inflammatory Responses of Critically-Ill Burn Patients (A Randomized Clinical Trial). In Proceedings of the Health Science International Conference (HSIC 2017); Atlantis Press: Amsterdam, The Netherlands, 2017; pp. 390–398. [Google Scholar]
- Besser, M.; Terberger, J.; Weber, L.; Ghebremedhin, B.; Naumova, E.A.; Arnold, W.H.; Stuermer, E.K. Impact of probiotics on pathogen survival in an innovative human plasma biofilm model (hpBIOM). J. Transl. Med. 2019, 17, 243. [Google Scholar] [CrossRef]
- Moreira, C.F.; Cassini-Vieira, P.; Canesso, M.C.C.; Felipetto, M.; Ranfley, H.; Teixeira, M.M.; Nicoli, J.R.; Martins, F.S.; Barcelos, L.S. Lactobacillus rhamnosus CGMCC 1.3724 (LPR) improves skin wound healing and reduces scar formation in mice. Probiotics Antimicrob. Proteins 2021, 13, 709–719. [Google Scholar] [CrossRef]
- Peyri, J. Topical bacteriotherapy of the skin. J. Cutan. Dis. 1912, 30, 688–689. [Google Scholar]
- Ming, Z.; Han, L.; Bao, M.; Zhu, H.; Qiang, S.; Xue, S.; Liu, W. Living bacterial hydrogels for accelerated infected wound healing. Adv. Sci. 2021, 8, 2102545. [Google Scholar] [CrossRef]
- Abootaleb, M.; Bandari, N.M.; Soleimani, N.A. Interference of Lactobacillus casei with Pseudomonas aeruginosa in the treatment of infected burns in Wistar rats. Iran. J. Basic Med. Sci. 2021, 24, 143–149. [Google Scholar] [CrossRef]
- Stanbro, J.; Park, J.M.; Bond, M.; Stockelman, M.G.; Simons, M.P.; Watters, C. Topical delivery of Lactobacillus culture supernatant increases survival and wound resolution in traumatic Acinetobacter baumannii infections. Probiotics Antimicrob. Proteins 2020, 12, 809–818. [Google Scholar] [CrossRef]
- Sinha, A.; Sagar, S.; Madhumathy, M.; Osborne, W.J. Probiotic bacteria in wound healing; an in-vivo study. Iran. J. Biotechnol. 2019, 17, 11–15. [Google Scholar] [CrossRef]
- Lukic, J.; Chen, V.; Strahinic, I.; Begovic, J.; Lev-Tov, H.; Davis, S.C.; Tomic-Canic, M.; Pastar, I. Probiotics or pro-healers: The role of beneficial bacteria in tissue repair. Wound Repair Regen. 2017, 25, 912–922. [Google Scholar] [CrossRef]
- Mohammed Saeed, W.; McBain, A.J.; Cruickshank, S.M.; O’Neill, C.A. Lactobacillus rhamnosus GG inhibits the toxic effects of Staphylococcus aureus on epidermal keratinocytes. Appl. Environ. Microbiol. 2014, 80, 5773–5781. [Google Scholar] [CrossRef]
- Al-Malkey, M.K.; Ismeeal, M.C.; Al-Hur, F.J.A.; Mohammed, S.W.; Nayyef, H.J. Antimicrobial effect of probiotic Lactobacillus spp. on Pseudomonas aeruginosa. J. Contemp. Med. Sci. 2017, 3, 218–223. [Google Scholar] [CrossRef]
- Lopes, E.G.; Moreira, D.A.; Gullón, P.; Gullón, B.; Cardelle-Cobas, A.; Tavaria, F.K. Topical application of probiotics in skin: Adhesion, antimicrobial and antibiofilm in vitro assays. J. Appl. Microbiol. 2017, 122, 450–461. [Google Scholar] [CrossRef]
- Chan, A.P.; Choi, Y.; Brinkac, L.M.; Krishnakumar, R.; DePew, J.; Kim, M.; Hinkle, M.K.; Lesho, E.P.; Fouts, D.E. Multidrug resistant pathogens respond differently to the presence of co-pathogen, commensal, probiotic and host cells. Sci. Rep. 2018, 8, 8656. [Google Scholar] [CrossRef]
- Li, Z.; Behrens, A.M.; Ginat, N.; Tzeng, S.Y.; Lu, X.; Sivan, S.; Langer, R.; Jaklenec, A. Biofilm-inspired encapsulation of probiotics for the treatment of complex infections. Adv. Mater. 2018, 30, 1803925. [Google Scholar] [CrossRef]
- Moghadam, S.S.; Khodaii, Z.; Zadeh, S.F.; Ghooshchian, M.; Aghmiyuni, Z.F.; Shabestari, T.M. Synergistic or antagonistic effects of probiotics and antibiotics-alone or in combination-on antimicrobial-resistant Pseudomonas aeruginosa isolated from burn wounds. Arch. Clin. Infect. Dis. 2018, 13, 2–4. [Google Scholar] [CrossRef]
- Onbas, T.; Osmanagaoglu, O.; Kiran, F. Potential properties of Lactobacillus plantarum F-10 as a bio-control strategy for wound infections. Probiotics Antimicrob. Proteins 2019, 11, 1110–1123. [Google Scholar] [CrossRef]
- Soleymanzadeh Moghadam, S.; Mohammad, N.; Ghooshchian, M.; FathiZadeh, S.; Khodaii, Z.; Faramarzi, M.; Fagheei Aghmiyuni, Z.; Roudbari, M.; Pazouki, A.; Mousavi Shabestari, T. Comparison of the effects of Lactobacillus plantarum versus imipenem on infected burn wound healing. Med. J. Islam. Repub. Iran 2020, 34, 94. [Google Scholar] [CrossRef]
- Shams Eldeen, M.A.; Elnahal, A.; Ads, A.; Elsawaf, M.; Samy, S.M. Effect of Lactobacillus plantarum on virulence factors of Pseudomonas aeruginosa isolated from wound infection. Microbes Infect. Dis. 2021, 2, 790–796. [Google Scholar] [CrossRef]
- Li, Z.; Zhang, S.; Zuber, F.; Altenried, S.; Jaklenec, A.; Langer, R.; Ren, Q. Topical application of Lactobacilli successfully eradicates Pseudomonas aeruginosa biofilms and promotes wound healing in chronic wounds. Microbes Infect. 2023, 25, 105176. [Google Scholar] [CrossRef]
- Argañaraz Aybar, J.N.; Ortiz Mayor, S.; Olea, L.; Garcia, J.J.; Nisoria, S.; Kolling, Y.; Melian, C.; Rachid, M.; Torres Dimani, R.; Werenitzky, C.; et al. Topical administration of Lactiplantibacillus plantarum accelerates the healing of chronic diabetic foot ulcers through modifications of infection, angiogenesis, macrophage Phenotype and neutrophil response. Microorganisms 2022, 10, 634. [Google Scholar] [CrossRef]
- Zielińska, M.; Pawłowska, A.; Orzeł, A.; Sulej, L.; Muzyka-Placzyńska, K.; Baran, A.; Filipecka-Tyczka, D.; Pawłowska, P.; Nowińska, A.; Bogusławska, J.; et al. Wound Microbiota and Its Impact on Wound Healing. Int. J. Mol. Sci. 2023, 24, 17318. [Google Scholar] [CrossRef]
- Bekiaridou, A.; Karlafti, E.; Oikonomou, I.M.; Ioannidis, A.; Papavramidis, T.S. Probiotics and Their Effect on Surgical Wound Healing: A Systematic Review and New Insights into the Role of Nanotechnology. Nutrients 2021, 13, 4265. [Google Scholar] [CrossRef]
- Kiousi, D.E.; Efstathiou, C.; Tzampazlis, V.; Plessas, S.; Panopoulou, M.; Koffa, M.; Galanis, A. Genetic and phenotypic assessment of the antimicrobial activity of three potential probiotic lactobacilli against human enteropathogenic bacteria. Front. Cell. Infect. Microbiol. 2023, 13, 1127256. [Google Scholar] [CrossRef] [PubMed]
- Menni, A.; Moysidis, M.; Tzikos, G.; Stavrou, G.; Tsetis, J.K.; Shrewsbury, A.D.; Filidou, E.; Kotzampassi, K. Looking for the Ideal Probiotic Healing Regime. Nutrients 2023, 15, 3055. [Google Scholar] [CrossRef]
- Landén, N.X.; Li, D.; Ståhle, M. Transition from inflammation to proliferation: A critical step during wound healing. Cell. Mol. Life Sci. 2016, 73, 3861–3885. [Google Scholar] [CrossRef]
- Campos, L.F.; Tagliari, E.; Casagrande, T.A.C.; Noronha, L.D.; Campos, A.C.L.; Matias, J.E.F. Effects of probiotics supplementation on skin wound healing in diabetic rats. Arq. Bras. Cir. Dig. 2020, 33, e1498. [Google Scholar] [CrossRef] [PubMed]
- Lombardi, F.; Augello, F.R.; Artone, S.; Bahiti, B.; Sheldon, J.M.; Giuliani, M.; Cifone, M.G.; Palumbo, P.; Cinque, B. Efficacy of probiotic Streptococcus thermophilus in counteracting TGF-β1-induced fibrotic response in normal human dermal fibroblasts. J. Inflamm. 2022, 19, 27. [Google Scholar] [CrossRef]
- Saravanan, P.; Pooja, R.; Balachander, N.; Kesav Ram Singh, K.; Silpa, S.; Rupachandra, S. Anti-inflammatory and wound healing properties of lactic acid bacteria and its peptides. Folia Microbiol. 2023, 68, 337–353. [Google Scholar] [CrossRef]
- Tanno, H.; Kanno, E.; Kurosaka, S.; Oikawa, Y.; Watanabe, T.; Sato, K.; Kasamatsu, J.; Miyasaka, T.; Ishi, S.; Shoji, M.; et al. Topical administration of heat-killed Enterococcus faecalis strain KH2 promotes re-epithelialization and granulation tissue formation during skin wound-healing. Biomedicines 2021, 9, 1520. [Google Scholar] [CrossRef]
- Hashim, Z.A.; Qasim, Z.S. Assessment of Saccharomyces boulardii effect on rats Staphylococcus aureus induced skin infection: An in-vivo study. J. Res. Pharm. 2022, 26, 1342–1351. [Google Scholar]
- Barzegari, A.A.; Hashemzaei, M.; Alihemmati, A.R. Positive Effects of Spray-Dried Streptococcus thermophilus on Healing of Second-Degree Burn Wounds in Wistar Rats. Med. Lab. J. 2019, 13, 23–29. [Google Scholar] [CrossRef]
- Oryan, A.; Alemzadeh, E.; Eskandari, M.H. Kefir Accelerates Burn Wound Healing through Inducing Fibroblast Cell Migration In Vitro and Modulating the Expression of IL-1ß, TGF-ß1, and bFGF Genes In Vivo. Probiotics Antimicrob. Proteins 2019, 11, 874–886. [Google Scholar] [CrossRef]
- Sangar, S.; Cheng, M.W.; Yu, Y. Probiotics for the treatment of other skin conditions (acne, psoriasis, seborrheic dermatitis, wounds, and skin cancer). In Probiotics in the Prevention and Management of Human Diseases; Elsevier Academic Press: Cambridge, MA, USA, 2022; pp. 129–137. [Google Scholar] [CrossRef]
- Twetman, S.; Pedersen, A.M.L.; Yucel-Lindberg, T. Probiotic supplements containing Lactobacillus reuteri does not affect the levels of matrix metalloproteinases and interferons in oral wound healing. BMC Res. Notes 2018, 11, 759. [Google Scholar] [CrossRef]
- Saputro, I.D.; Putra, O.N.; Pebrianton, H. Effects of probiotic administration on IGA and IL-6 level in severe burn patients: A randomized trial. Ann. Burn. Fire Disasters 2019, 32, 70. [Google Scholar]
- Navarro-López, V.; Martínez-Andrés, A.; Ramírez-Boscá, A.; Ruzafa-Costas, B.; Núñez-Delegido, E.; Carrión-Gutiérrez, M.A.; Prieto-Merino, D.; Codoñer-Cortés, F.; Ramón-Vidal, D.; Genovés-Martínez, S.; et al. Efficacy and safety of oral administration of a mixture of probiotic strains in patients with psoriasis: A randomized controlled clinical trial. Acta Derm.-Venereol. 2019, 99, 1078–1084. [Google Scholar] [CrossRef]
- Kotzampassi, K. Why give my surgical patients probiotics. Nutrients 2022, 14, 4389. [Google Scholar] [CrossRef]
- Thoma, G.; Stavrou, G.; Malliou, P.; Giamarellos-Bourboulis, E.; Kotzampassi, K. OR06: The use of probiotics as a preventative measure against surgical site infections in multiple trauma ICU patients: A preliminary study. Clin. Nutr. 2019, 38, S6. [Google Scholar] [CrossRef]
- Meenakshi, S.; Santhanakumar, R. The role of probiotics as wound healers: An overall view. J. Wound Care 2023, 32, 318–328. [Google Scholar] [CrossRef] [PubMed]
- Hou, K.; Wu, Z.X.; Chen, X.Y.; Wang, J.Q.; Zhang, D.; Xiao, C.; Zhu, D.; Koya, J.B.; Wei, L.; Li, J.; et al. Microbiota in health and diseases. Signal Transduct. Target Ther. 2022, 7, 135. [Google Scholar] [CrossRef] [PubMed]
- Nezamdoost-Sani, N.; Khaledabad, M.A.; Amiri, S.; Khaneghah, A.M. Alginate and derivatives hydrogels in encapsulation of probiotic bacteria: An updated review. Food Biosci. 2023, 52, 102433. [Google Scholar] [CrossRef]
- Kim, J.S.; Yu, H.; Woo, M.R.; Kim, D.W.; Kim, J.O.; Ku, S.K.; Jin, S.G.; Choi, H.G. Influence of hydrophilic polymers on mechanical property and wound recovery of hybrid bilayer wound dressing system for delivering thermally unstable probiotic. Biomater. Adv. 2022, 135, 112696. [Google Scholar] [CrossRef]
- Wang, X.; Gao, S.; Yun, S.; Zhang, M.; Peng, L.; Li, Y.; Zhou, Y. Micoencapsulating Alginate-Based Polymers for Probiotics Delivery Systems and Their Application. Pharmaceuticals 2022, 15, 644. [Google Scholar] [CrossRef]
- Kapoor, D.U.; Garg, R.; Gaur, M.; Pareek, A.; Prajapati, B.G.; Castro, G.R.; Suttiruengwong, S.; Sriamornsak, P. Pectin hydrogels for controlled drug release: Recent developments and future prospects. Saudi Pharm. J. SPJ Off. Publ. Saudi Pharm. Soc. 2022, 32, 102002. [Google Scholar] [CrossRef] [PubMed]
- Farahani, F.H.; Moraffah, F.; Samadi, N.; Sharifzadeh, M.; Motasadizadeh, H.; Vatanara, A. Improved infectious burn wound healing by applying lyophilized particles containing probiotics and prebiotics. Int. J. Pharm. 2023, 636, 122800. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.; Li, Y.; Song, J.; Zhou, L.; Wu, K.; Lu, X.; Zhai, X.; Wan, Z.; Gao, J. Highly active probiotic hydrogels matrixed on bacterial EPS accelerate wound healing via maintaining stable skin microbiota and reducing inflammation. Bioact. Mater. 2024, 35, 31–44. [Google Scholar] [CrossRef]
- Kaur Sandhu, S.; Raut, J.; Kumar, S.; Singh, M.; Ahmed, B.; Singh, J.; Rana, V.; Rishi, P.; Ganesh, N.; Dua, K.; et al. Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing. Int. J. Pharm. 2023, 643, 123187. [Google Scholar] [CrossRef]
In Vivo Model/Clinical Trial | Probiotics Used | Method of Administration | Effects Observed in Wound Healing | Intended Application | References |
---|---|---|---|---|---|
Swiss mice with excisional skin wounds | L. johnsonii LA1, L. paracasei ST11, and L. rhamnosus LPR | Oral gavage | Oral gavage administration of L. rhamnosus LPR enhanced wound healing by promotion of reepithelization process and angiogenesis, decreased leukocyte infiltration and granulation tissue. | Oral treatment with probiotics for stimulating wound healing | Moreira et al., 2021 [39] |
Wistar rats with experimentally induced wounds | Probiotic mix: L. paracasei 37, L. rhamnsus HN001, B. lactis HN0019, L. acidophilus NCFM | Oral administration of probiotics (dose: 250 mg/day). | The reduced expression of IL-17, IL-6, TNF-α (Tumour Necrosis Factor α), and TGF-β (Transforming Growth Factor β) improved wound healing and induced faster recovery. The decreased inflammatory process accelerated the deposition of collagen and fibrosis phase. | Oral treatment with probiotics for stimulating wound healing | Tagliari et al., 2022 [29] |
Clinical trial: females with episiotomy | Capsules of Lactobacillus casei 431 (once a day, for two weeks) | Oral administration of probiotic capsules | Orally ingested probiotics stimulated the wound healing process through angiogenic effects and anti-inflammatory properties. | Oral supplementation of probiotics as adjuvants in wound healing | Abdollahpour et al., 2023 [33] |
Clinical trial: burn patients | L. rhamnosus, L. delbrueckii subsp. Bulgaricus, L. acidophilus, L. casei, Streptococcus salivarus subsp. Thermophilus, B. breve, B. longum | Oral supplementation in form of capsules | Promoted immune response by reducing neutrophil and leucocyte levels; antimicrobial properties against burn wound pathogens; improved wound healing process. | Orally ingested probiotics for improving burn wound healing | Putra et al., 2017 [37] |
Clinical trial: pediatric patients with surgical interventions | L. rhamnosus GG ATCC 53103 | Oral-route administration as drops | Reduced the duration of antibiotic-associated diarrhea, frequency of dressing change, and incidence of postoperative wound complications. | Oral probiotics used as complementary therapy for management of complications which may occur after surgical intervention. | Esposito et al., 2018 [36] |
Clinical trial: oral mucosa injuries | L. reuteri (DSM 17938 and ATCC PTA 5289) | Oral administration of probiotics in form of lozenges | Alleviated clinical symptoms, less tissue swelling. | Alternative therapy with oral probiotics | Wälivaara et al., 2019 [34] |
Clinical trial: diabetic foot ulcer (DFU) | L. fermentum, L. acidophilus, L.casei, B. bifidum | Oral administration of probiotics mix incorporated in capsules | Probiotics reduced the ulcer length and improved parameters associated with healing process. | Oral supplementation for symptom alleviation in DFU patients | Mohseni et al., 2018 [35] |
Type of Study | Efficient against Wound Pathogen | Probiotics Used | Method of Evaluation | Effects | Intended Application | References |
---|---|---|---|---|---|---|
In vitro study | S. aureus | Lysate or spent culture fluid of L. rhamnosus GG, ATCC 53103, L. reuteri (ATCC 55730), and L. salivarius (UCC118) | Co-culture assays of normal human epidermal keratinocytes (NHEK). | Stimulate bacteriocins production, which enhances antimicrobial effects. | Topical therapy for wound infections. | Mohammedsaed et al., 2014 [46] |
In vitro study | P. aeruginosa isolated from burn and wound infections | L. rhamnosus GG, L. acidophilus | Well diffusion method. | Enhanced antimicrobial effects of bacteriocins produced by probiotics. | Prevention and treatment of wound infections. | Al-Malkey et al., 2017 [47] |
In vitro study | E. coli, P. aeruginosa, Propionibacterium acnes | Supernatants of L. delbrueckii, L. brevis D-24, L. acidophilus La-5, L-10, L-26, L. plantarum 226v, L. casei 20021 L.salivarius 20555, B. animalis Bb12, B. lactis B-94, B. longum 20088 | Well diffusion method. | Antibiofilm effects against tested pathogens; inhibition of bacterial adherence. | Topical application to restore cutaneous dysbiosis. | Lopes et al., 2017 [48] |
In vitro study | Enterobacter hormaechei, K. pneumoniae, A. baumannii | L. reuteri SD2112 | Co-culture with human diploid cells. | Inhibition of bacterial adherence. | Topical application for improving the management of open wounds and burns. | Chan et al., 2018 [49] |
In vitro study | P. aeruginosa S. aureus | L. acidophilus CL1285, L. casei LBC80R, L. rhamnosus CLR2 | Co-culture assays. Encapsulation of probiotics. | The encapsulation of probiotics in combination with antibiotics promoted complete eradication of tested pathogens | Topical co-administration with antibiotics, to increase their efficiency. | Li et al., 2018 [50] |
In vitro study | P. aeruginosa | L. reuteri DSM17938, L. acidophilus DSM, Bacillus coagulans, L. plantarum 299v, B. bifidum DSM20456 | Well diffusion method. | Some combinations of probiotics and antibiotics manifested synergistic effects. | Treatment of wounds through combination of probiotics and antibiotics for a better outcome. | Moghadam et al., 2018 [51] |
In vitro study | P. aeruginosa, S. aureus MRSA (Methicillin-resistant S. aureus) | Supernatant solution of L. plantarum F10 | Well diffusion method. Co-culture assays. | Biofilm inhibition effects. | Improving the treatment of cutaneous infections. | Onbas et al., 2019 [52] |
1. Skin from dorsal part of domestic farm pig (ex vivo). 2. Rat wound model (in vivo) | S. aureus | Protein-rich fraction of L. plantarum USM8613 isolated from meat products | Topically treated wound infections inoculated with S. aureus. | Promoted wound healing by stimulating the synthesis of chemokines and cytokines such as TNF—γ, INF—α, IL—4, IL—6, and β-defensin expression through all the healing stages. Stimulated keratinocytes migration rate. Reduced S. aureus infection at wound sites through autolysis process. | Topically treatment of probiotics in infected wounds. | Ong et al., 2019 [30] |
Immunocompromised wound mice | A. baumanii MDR (Multidrug resistant) clinical isolates | Supernatant of L. acidophilus ATCC 4356, L. casei ATCC 393, L. reuteri ATCC 23272 | Topically treatment of A. baumanii infected wounds. | Enhanced wound closure. Growth inhibition of planktonic cells. | Topical therapy for enhancing wound closure. | Stanbro et al., 2019 [43] |
1. In vitro study. 2. In vivo Wistar rats wound model | S. aureus MTCC No-3160 | Probiotic gel formulation and supernatant solution of Lactobacillus VITSAMJ1 (isolated from goat milk) | Agar-well diffusion method. Topically treated infections with probiotic gel formulation (twice a day). | Prevention of wound infection through synthesis of antimicrobial substances, which inhibit bacterial adhesion to epithelial tissue. The probiotic gel formulation reduced the size of the wound, accelerated the healing process by promoting angiogenesis and inflammatory responses. | Development of a topical product for enhanced wound healing. | Sinha et al., 2019 [44] |
1. In vitro study. 2. In vivo Wistar rats wound model | P. aeruginosa clinically isolated from burn wounds and P.aeruginosa ATCC 27853 | Supernatant of Bacillus coagulans (DSM1), B. bifidum (DSM20456) and L. plantarum 299v (DSM9843), L. salivarius ES1, L. reuteri ES10 and L. salivarius ES8 | Disk diffusion method (NCCLS) Topical wound treatment. | Inhibition of P. aeruginosa growth. Promoted wound closure and significantly reduced wound size. | Improved topical wound treatment. | Moghadam et al., 2020 [53] |
In vivo Wistar rats wound model | P. aeruginosa MDR clinical isolates from patients with burn wounds | Supernatant of L. casei PTCC 1608—spray | Topical treatment (wounds were sprayed every day for 28 days). | Anti-adhesion effects on tested bacterial strains. Fibrogenesis process stimulation. | Improved topical therapy for wound infections caused by MDR P. aeruginosa. | Abootaleb et al., 2021 [42] |
In vitro study | P. aeruginosa strains clinically isolated from patients with wound infections | L. plantarum | In vitro treatment of pathogen agents with probiotics. | Modulation of P. aeruginosa virulence factor production (elastase and pyocyanin). | Improved topical therapy of P. aeruginosa wound infections. | Shams Eldeen et al., 2021 [54] |
1. In vitro study. 2. Wound models in Wistar rats | E. coli, S. aureus, and Salmonella spp. | L. reuteri encapsulated in hydrogels | Well diffusion method. Co-culture assays. Topically treated wound infections in rats. | Antibacterial activity in vitro and in vivo. Antibiofilm properties in vivo. Stimulated wound healing, promoted collagen deposition (in vivo). | Hydrogels dressings for topically treatment of infected wounds | Ming et al., 2021 [41] |
Ex vivo skin model (culture of human dermal fibroblasts, HDFs) | P. aeruginosa biofilms | Capsules containing L. acidophilus CL128, L. rhamnosus CLR2, and L. casei LBC80R | In vitro biofilm assay Co-culture (probiotics—HDFs) | Probiotics treatment stimulated cell migration and eradicated preformed biofilms (in vitro), decreased the bioburden in wound infection (ex vivo). | Direct application of probiotics and probiotic wound dressings for improving wound healing. | Li et al., 2023 [55] |
Clinical Trials (patients with diabetic foot ulcer) | Streptococcus sp., Stpahylococcus sp., P. aeruginosa biofilms | L. plantarum ATCC 10241 | Topical application on the wounds. | Probiotics improved angiogenesis in the skin tissues of patients with diabetes mellitus and diabetic foot ulcer, while reducing microbial load on site. | Adjuvant to surgical debridement to accelerate healing process. | Argañaraz Aybar et al., 2022 [56] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bădăluță, V.A.; Curuțiu, C.; Dițu, L.M.; Holban, A.M.; Lazăr, V. Probiotics in Wound Healing. Int. J. Mol. Sci. 2024, 25, 5723. https://doi.org/10.3390/ijms25115723
Bădăluță VA, Curuțiu C, Dițu LM, Holban AM, Lazăr V. Probiotics in Wound Healing. International Journal of Molecular Sciences. 2024; 25(11):5723. https://doi.org/10.3390/ijms25115723
Chicago/Turabian StyleBădăluță, Valentina Alexandra, Carmen Curuțiu, Lia Mara Dițu, Alina Maria Holban, and Veronica Lazăr. 2024. "Probiotics in Wound Healing" International Journal of Molecular Sciences 25, no. 11: 5723. https://doi.org/10.3390/ijms25115723
APA StyleBădăluță, V. A., Curuțiu, C., Dițu, L. M., Holban, A. M., & Lazăr, V. (2024). Probiotics in Wound Healing. International Journal of Molecular Sciences, 25(11), 5723. https://doi.org/10.3390/ijms25115723