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Journals / Fenerbahçe Üniversitesi Sağlık Bilimleri Dergisi / 2026 / Cilt: 6 Sayı: 1

Probiotics in the Prevention and Management of Antibiotic-Resistant Infections

Antibiyotik Dirençli Enfeksiyonların Önlenmesi ve Yönetiminde Probiyotikler

Mahdi Marzi(FENERBAHÇE ÜNİVERSİTESİ)0000-0002-8518-0818
Ayşe Karacalı Tunç(IĞDIR ÜNİVERSİTESİ)0000-0002-6453-9887
Pages
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Publication Date
2026-05-20
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Their integration into One Health-based antimicrobial-stewardship and precision-medicine frameworks may help restore long-term microbiome equilibrium and reduce global antibiotic dependence.

📌 3 Key Takeaways

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Objective & Hypothesis:Antimicrobial resistance (AMR) represents one of the most critical global health threats of the twenty-first century, responsible for more than one million deaths annually and projected to cause ten million by 2050.
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Key Findings & Data:The overuse and misuse of antibiotics in human medicine, veterinary practice, and agriculture have accelerated the emergence of multidrug-resistant (MDR) pathogens, severely limiting therapeutic options—particularly in intensive care and oncology settings.
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Conclusion & Impact:Their integration into One Health-based antimicrobial-stewardship and precision-medicine frameworks may help restore long-term microbiome equilibrium and reduce global antibiotic dependence.
🔬Design:Review & Systematic Survey
📍Scope:2050 Verileri
⚙️Variables:Antimikrobiyal Direnç · Probiyotikler · Postbiyotikler

Abstract

Antimicrobial resistance (AMR) represents one of the most critical global health threats of the twenty-first century, responsible for more than one million deaths annually and projected to cause ten million by 2050. The overuse and misuse of antibiotics in human medicine, veterinary practice, and agriculture have accelerated the emergence of multidrug-resistant (MDR) pathogens, severely limiting therapeutic options—particularly in intensive care and oncology settings. In this narrative review, we aimed to integrate mechanistic, translational, and clinical evidence on the preventive and therapeutic roles of probiotics in combating antibiotic-resistant infections. Peer-reviewed literature from 2010 to 2025 was analyzed to summarize current knowledge on molecular mechanisms, clinical efficacy, safety, and regulatory frameworks. Probiotics act through multiple complementary pathways, including competitive exclusion of pathogens, production of antimicrobial metabolites, reinforcement of epithelial-barrier integrity, modulation of immune responses, and disruption of biofilm formation. Randomized clinical trials demonstrate that specific strains—such as Saccharomyces boulardii, Lactobacillus rhamnosus GG, and Bifidobacterium longum—reduce the incidence of antibiotic-associated diarrhea, Clostridioides difficile infection, ventilator-associated pneumonia, and urinary tract infections caused by MDR organisms. Meta-analyses further confirm their role in restoring gut microbial diversity following antibiotic therapy. Probiotics, postbiotics, and next-generation microbiome therapeutics hold significant promise as adjunctive strategies within antimicrobial-resistance management. Their integration into One Health-based antimicrobial-stewardship and precision-medicine frameworks may help restore long-term microbiome equilibrium and reduce global antibiotic dependence.

Özet

Antimikrobiyal direnç (AMR), yirmi birinci yüzyılın en ciddi küresel sağlık tehditlerinden birini temsil etmektedir. Her yıl bir milyondan fazla ölüme neden olmakta ve 2050 yılına kadar bu sayının on milyona ulaşacağı öngörülmektedir. İnsan tıbbında, veteriner uygulamalarda ve tarımda antibiyotiklerin aşırı ve yanlış kullanımı, çoklu ilaç direncine sahip (MDR) patojenlerin ortaya çıkışını hızlandırmış; bu durum özellikle yoğun bakım ve onkoloji alanlarında tedavi seçeneklerini ciddi biçimde kısıtlamıştır. Bu anlatı derlemede, antibiyotiğe dirençli enfeksiyonlarla mücadelede probiyotiklerin önleyici ve tedavi edici rollerine ilişkin mekanistik, translasyonel ve klinik kanıtları bütünleştirmeyi amaçladık. 2010–2025 yılları arasındaki hakemli literatür incelenerek moleküler mekanizmalar, klinik etkinlik, güvenlilik ve düzenleyici çerçeveler hakkındaki güncel bilgiler özetlenmiştir. Probiyotikler; patojenlerin rekabetçi dışlanması, antimikrobiyal metabolitlerin üretimi, epitel bariyer bütünlüğünün güçlendirilmesi, bağışıklık yanıtlarının düzenlenmesi ve biyofilm oluşumunun engellenmesi gibi çoklu ve birbirini tamamlayan yollarla etki gösterir. Randomize klinik çalışmalar, Saccharomyces boulardii, Lactobacillus rhamnosus GG ve Bifidobacterium longum gibi belirli suşların; antibiyotik ilişkili ishal, Clostridioides difficile enfeksiyonu, ventilatörle ilişkili pnömoni ve çoklu ilaç dirençli mikroorganizmaların neden olduğu idrar yolu enfeksiyonlarının görülme sıklığını azalttığını göstermektedir. Meta-analizler, ayrıca antibiyotik tedavisini takiben bağırsak mikrobiyota çeşitliliğinin yeniden sağlanmasında bu mikroorganizmaların rolünü doğrulamaktadır. Probiyotikler, postbiyotikler ve yeni nesil mikrobiyom temelli tedaviler, antimikrobiyal direnç yönetimi kapsamında tamamlayıcı stratejiler olarak önemli bir potansiyel taşımaktadır. Bu yaklaşımların, Tek Sağlık (One Health) temelli antimikrobiyal gözetim ve hassas tıp (precision medicine) çerçevelerine entegre edilmesi, uzun vadede mikrobiyom dengesinin yeniden kurulmasına ve küresel antibiyotik bağımlılığının azaltılmasına katkı sağlayabilir.

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Cite This Article

Marzi, M., Tunç, A. K. (2026). Probiotics in the Prevention and Management of Antibiotic-Resistant Infections. Fenerbahçe Üniversitesi Sağlık Bilimleri Dergisi, Cilt: 6 Sayı: 1. https://doi.org/10.56061/fbujohs.1817657

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References (111)

  1. World Health Organization. (2023, November 21). Antimicrobial resistance: Fact sheet. Geneva: World Health Organization. Retrieved January 10, 2025, from https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
  2. Antimicrobial Resistance Collaborators. (2022). Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. The Lancet, 399(10325), 629–655. https://doi.org/10.1016/S0140-6736(21)02724-0
  3. GBD 2021 Antimicrobial Resistance Collaborators. (2024). Global burden of bacterial antimicrobial resistance 1990–2021: A systematic analysis with forecasts to 2050. The Lancet, 404(10459), 1199–1226. https://doi.org/10.1016/S0140-6736(24)01867-1
  4. World Health Organization. (2024, June 14). 2023 antibacterial agents in clinical and preclinical development: An overview and analysis. Geneva: World Health Organization. Retrieved October 21, 2025, from https://www.who.int/publications/i/item/9789240094000
  5. Jesudason, T. (2024). Antibacterial agents in preclinical and clinical development. The Lancet Microbe, 5(10), 100962. https://doi.org/10.1016/j.lanmic.2024.100962
  6. Bratkovič, T., Zahirović, A., Bizjak, M., Rupnik, M., Štrukelj, B., & Berlec, A. (2024). New treatment approaches for Clostridioides difficile infections: Alternatives to antibiotics and fecal microbiota transplantation. Gut Microbes, 16(1), 2337312. https://doi.org/10.1080/19490976.2024.2337312
  7. Food and Agriculture Organization of the United Nations & World Health Organization. (2002). Guidelines for the evaluation of probiotics in food: Report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food. London, Ontario: FAO/WHO. Retrieved October 21, 2025, from https://www.fao.org/3/a0512e/a0512e.pdf
  8. Dempsey, E., & Corr, S. C. (2022). Lactobacillus spp. for gastrointestinal health: Current and future perspectives. Frontiers in Immunology, 13, 840245. https://doi.org/10.3389/fimmu.2022.840245
  9. Chandrasekaran, P., Weiskirchen, S., & Weiskirchen, R. (2024). Effects of probiotics on gut microbiota: An overview. International Journal of Molecular Sciences, 25(11), 6022. https://doi.org/10.3390/ijms25116022
  10. Xiao, M., Zhang, C., Duan, H., Narbad, A., Zhao, J., Chen, W., Zhai, Q., Yu, L., & Tian, F. (2024). Cross-feeding of bifidobacteria promotes intestinal homeostasis: A lifelong perspective on the host health. NPJ Biofilms and Microbiomes, 10(1), 47. https://doi.org/10.1038/s41522-024-00524-6
  11. Lathakumari, R. H., Vajravelu, L. K., Satheesan, A., Ravi, S., & Thulukanam, J. (2024). Antibiotics and the gut microbiome: Understanding the impact on human health. Medical Microecology, 20, 100106. https://doi.org/10.1016/j.medmic.2024.100106
  12. Chang, K. C., Nagarajan, N., & Gan, Y. H. (2024). Short-chain fatty acids of various lengths differentially inhibit Klebsiella pneumoniae and Enterobacteriaceae species. mSphere, 9(2), e00781–23. https://doi.org/10.1128/msphere.00781-23
  13. Pothoulakis, C., Kelly, C. P., Joshi, M. A., Gao, N., O’Keane, C. J., Castagliuolo, I., & Lamont, J. T. (1993). Saccharomyces boulardii inhibits Clostridium difficile toxin A binding and enterotoxicity in rat ileum. Gastroenterology, 104(4), 1108–1115. https://doi.org/10.1016/0016-5085(93)90280-P
  14. Montassier, E., Valdés-Mas, R., Batard, E., Zmora, N., Dori-Bachash, M., Suez, J., & Elinav, E. (2021). Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner. Nature Microbiology, 6(8), 1043–1054. https://doi.org/10.1038/s41564-021-00920-0
  15. John, D., Michael, D., Dabcheva, M., Hulme, E., Illanes, J., Webberley, T., Wang, D., & Plummer, S. (2024). A double-blind, randomized, placebo-controlled study assessing the impact of probiotic supplementation on antibiotic-induced changes in the gut microbiome. Frontiers in Microbiomes, 3, 1359580. https://doi.org/10.3389/frmbi.2024.1359580
  16. Karczewski, J., Troost, F. J., Konings, I., Dekker, J., Kleerebezem, M., Brummer, R. J., & Wells, J. M. (2010). Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. American Journal of Physiology - Gastrointestinal and Liver Physiology, 298(6), G851–G859. https://doi.org/10.1152/ajpgi.00327.2009
  17. Whitmore, M., Tobin, I., Burkardt, A., & Zhang, G. (2024). Nutritional modulation of host defense peptide synthesis: A novel host-directed antimicrobial therapeutic strategy? Advances in Nutrition, 15(9), 100277. https://doi.org/10.1016/j.advnut.2024.100277
  18. Litton, E., Anstey, M., Broadhurst, D., Chapman, A., Currie, A., Ferrier, J., … (2021). Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: The randomized, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT). Intensive Care Medicine, 47(3), 307–315. https://doi.org/10.1007/s00134-020-06322-w
  19. Szajewska, H., & Kołodziej, M. (2015). Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Alimentary Pharmacology & Therapeutics, 42(7), 793–801. https://doi.org/10.1111/apt.13344
  20. Horrocks, V., & McDonald, J. A. K. (2023). Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization. Microbiology, 169(8), 001377. https://doi.org/10.1099/mic.0.001377
  21. Hudcovic, T., Hermanova, P., Kozakova, H., Benada, O., Kofronova, O., Schwarzer, M., & Srutkova, D. (2024). Priority order of neonatal colonization by a probiotic or pathogenic Escherichia coli strain dictates the host response to experimental colitis. Frontiers in Microbiology, 15, 1393732. https://doi.org/10.3389/fmicb.2024.1393732
  22. Monteagudo-Mera, A., Rastall, R. A., Gibson, G. R., Charalampopoulos, D., & Chatzifragkou, A. (2019). Adhesion mechanisms mediated by probiotics and prebiotics and their potential impact on human health. Applied Microbiology and Biotechnology, 103(16), 6463–6472. https://doi.org/10.1007/s00253-019-09978-7
  23. Sadeghpour Heravi, F. (2024). Host–vaginal microbiota interaction: Shaping the vaginal microenvironment and bacterial vaginosis. Current Clinical Microbiology Reports, 11, 177–191. https://doi.org/10.1007/s40588-024-00227-8
  24. Spiga, L., Fansler, R. T., Perera, Y. R., Shealy, N. G., Munneke, M. J., David, H. E., Torres, T. P., Lemoff, A., Ran, X., Richardson, K. L., Pudlo, N., Martens, E. C., Folta-Stogniew, E., Yang, Z. J., Skaar, E. P., Byndloss, M. X., Chazin, W. J., & Zhu, W. (2023). Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection. Cell Host & Microbe, 31(10), 1639–1654.e10. https://doi.org/10.1016/j.chom.2023.08.018
  25. Fernandes, A., & Jobby, R. (2022). Bacteriocins from lactic acid bacteria and their potential clinical applications. Applied Biochemistry and Biotechnology, 194(10), 4377–4399. https://doi.org/10.1007/s12010-022-03870-3
  26. Huang, F., Zhang, J., Ma, Y., … (2024). Unraveling the antimicrobial potential of Lactiplantibacillus plantarum strains. Frontiers in Microbiology, 15, 1347830. https://doi.org/10.3389/fmicb.2024.1347830
  27. Birri, D. J., Brede, D. A., & Nes, I. F. (2012). Salivaricin D, a novel intrinsically trypsin-resistant lantibiotic produced by Streptococcus salivarius. Applied and Environmental Microbiology, 78(2), 402–410. https://doi.org/10.1128/AEM.06588-11
  28. Heesemann Rosenkilde, C. E., Lützhøft, D. O., Vazquez-Uribe, R., & Sommer, M. O. A. (2024). Heterologous expression and antimicrobial potential of class II bacteriocins against representative gut microbiota species. Gut Microbes, 16(1), 2369338. https://doi.org/10.1080/19490976.2024.2369338
  29. Takano, T., Kudo, H., Eguchi, S., Matsumoto, A., Oka, K., Yamasaki, Y., Takahashi, M., Koshikawa, T., Takemura, H., Yamagishi, Y., Mikamo, H., & Kunishima, H. (2023). Inhibitory effects of vaginal Lactobacilli on Candida albicans growth, hyphal formation, biofilm development, and epithelial cell adhesion. Frontiers in Cellular and Infection Microbiology, 13, 1113401. https://doi.org/10.3389/fcimb.2023.1113401
  30. Hajfarajollah, H., Eslami, P., Mokhtarani, B., & Akbari Noghabi, K. (2018). Biosurfactants from probiotic bacteria: A review. Biotechnology and Applied Biochemistry, 65(6), 768–783. https://doi.org/10.1002/bab.1686
  31. Sepehr, A., Miri, S. T., Aghamohammad, S., Rahimirad, N., Milani, M., Pourshafie, M.-R., & Rohani, M. (2024). Health benefits, antimicrobial activities, and potential applications of probiotics: A review. Medicine (Baltimore), 103(52), e32412. https://doi.org/10.1097/MD.0000000000032412
  32. Mazziotta, C., Tognon, M., Martini, F., Torreggiani, E., & Rotondo, J. C. (2023). Probiotics mechanism of action on immune cells and beneficial effects on human health. Cells, 12(1), 184. https://doi.org/10.3390/cells12010184
  33. Ullah, H., Arbab, S., Tian, Y., Chen, Y., Liu, C.-Q., Li, Q., & Li, K. (2024). Crosstalk between gut microbiota and host immune system and its response to traumatic injury. Frontiers in Immunology, 15, 1413485. https://doi.org/10.3389/fimmu.2024.1413485
  34. Haque, M., Al-Sadi, R., Youssef, M., … (2024). Lactobacillus acidophilus inhibits the TNF-α-induced increase in intestinal epithelial tight junction permeability via a TLR-2 and PI3K-dependent inhibition of NF-κB activation. Frontiers in Immunology, 15, 1348010. https://doi.org/10.3389/fimmu.2024.1348010
  35. Li, W., Zhang, S., Wang, Y., Bian, H., Yu, S., Huang, L., & Ma, W. (2023). Complex probiotics alleviate ampicillin-induced antibiotic-associated diarrhea in mice. Frontiers in Microbiology, 14, 1156058. https://doi.org/10.3389/fmicb.2023.1156058
  36. Saini, P., Ayyanna, R., Kumar, R., Bhowmick, S. K., Bhaskar, V., & Dey, B. (2024). Restriction of growth and biofilm formation of ESKAPE pathogens by caprine gut-derived probiotic bacteria. Frontiers in Microbiology, 15, 1428808. https://doi.org/10.3389/fmicb.2024.1428808
  37. Mouafo, H. T., Sokamte, A. T., Manet, L., Mbarga, A. J. M., Nadezdha, S., Devappa, S., & Mbawala, A. (2023). Biofilm inhibition, antibacterial and antiadhesive properties of a novel biosurfactant from Lactobacillus paracasei N2 against multi-antibiotics-resistant pathogens isolated from braised fish. Fermentation, 9(7), 646. https://doi.org/10.3390/fermentation9070646
  38. Che, J., Wu, J., Chen, Z., Liu, S., Sun, G., Chen, G., Zhao, T., He, Y., & Yin, L. (2024). Elimination of pathogen biofilms via postbiotics from lactic acid bacteria: A promising method in food and biomedicine. Microbiology Spectrum, 12(2), e02567–23. https://doi.org/10.1128/spectrum.02567-23
  39. Valenzuela Ruiz, V., Gándara-Ledezma, A., Villarreal-Delgado, M. F., Villa-Rodríguez, E. D., Parra-Cota, F. I., Santoyo, G., Gómez-Godínez, L. J., Cira Chávez, L. A., & de los Santos-Villalobos, S. (2024). Regulation, biosynthesis, and extraction of Bacillus-derived lipopeptides and its implications in biological control of phytopathogens. Stresses, 4(1), 107–132. https://doi.org/10.3390/stresses4010007
  40. Davares, A. K. L., Arsene, M. M. J., Podoprigora, I. V., Yashina, N. V., Zhigunova, A. V., Vasilyeva, E. A., … (2022). Quorum-sensing inhibitors from probiotics as a strategy to combat bacterial cell-to-cell communication involved in food spoilage and food safety. Fermentation, 8(12), 711. https://doi.org/10.3390/fermentation8120711
  41. Al-Saafin, B. A., Al-Bakri, A. G., Abdelrazig, S., & Dahabiyeh, L. A. (2023). Investigating the effect of the probiotic Lactobacillus plantarum and the prebiotic fructooligosaccharides on Pseudomonas aeruginosa metabolome, virulence factors, and biofilm formation as potential quorum sensing inhibitors. Microbial Pathogenesis, 177, 106057. https://doi.org/10.1016/j.micpath.2023.106057
  42. Rodrigues, L., van der Mei, H., Banat, I. M., Teixeira, J., & Oliveira, R. (2006). Inhibition of microbial adhesion to silicone rubber treated with biosurfactant from Streptococcus thermophilus A. FEMS Immunology and Medical Microbiology, 46(1), 107–112. https://doi.org/10.1111/j.1574-695X.2005.00006.x
  43. Guo, Q., Goldenberg, J. Z., Humphrey, C., El Dib, R., & Johnston, B. C. (2019). Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database of Systematic Reviews, 2019(4), CD004827. https://doi.org/10.1002/14651858.CD004827.pub5
  44. Salvati, F., Catania, F., Murri, R., Fantoni, M., & Torti, C. (2024). Clostridioides difficile infection: An update. Infection Medicine, 32(3), 280–291. https://doi.org/10.53854/liim-3203-3
  45. Johnston, B. C., Ma, S. S., Goldenberg, J. Z., Thorlund, K., Vandvik, P. O., Loeb, M., & Guyatt, G. H. (2012). Probiotics for the prevention of Clostridium difficile-associated diarrhea: A systematic review and meta-analysis. Annals of Internal Medicine, 157(12), 878–888. https://doi.org/10.7326/0003-4819-157-12-201212180-00563
  46. Leal, J. R., Heitman, S. J., Conly, J. M., Henderson, E. A., & Manns, B. J. (2016). Cost-effectiveness analysis of the use of probiotics for the prevention of Clostridium difficile-associated diarrhea in a provincial healthcare system. Infection Control & Hospital Epidemiology, 37(9), 1079–1086. https://doi.org/10.1017/ice.2016.134
  47. McFarland, L. V., Surawicz, C. M., Greenberg, R. N., Fekety, R., Elmer, G. W., Moyer, K. A., Melcher, S. A., Bowen, K. E., Cox, J. L., & Noorani, Z. (1994). A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA, 271(24), 1913–1918. https://doi.org/10.1001/jama.271.24.1913
  48. Rahman, M. N., Barua, N., Tin, M. C. F., Dharmaratne, P., Wong, S. H., & Ip, M. (2024). The use of probiotics and prebiotics in decolonizing pathogenic bacteria from the gut: A systematic review and meta-analysis of clinical outcomes. Gut Microbes, 16(1), 2356279. https://doi.org/10.1080/19490976.2024.2356279
  49. Zhang, H. J., Wang, H. W., Tian, F. Y., Yang, C. Z., Zhao, M., Ding, Y. X., Wang, X. Y., & Cui, X. Y. (2024). Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: A systematic review and meta-analysis. Scientific Reports, 14(1), 24349. https://doi.org/10.1038/s41598-024-75791-6
  50. Panigrahi, P., Parida, S., Nanda, N. C., Satpathy, R., Pradhan, L., Chandel, D. S., Baccaglini, L., Mohapatra, A., Mohapatra, S. S., Misra, P. R., Chaudhry, R., Chen, H. H., Johnson, J. A., Morris, J. G., Paneth, N., & Gewolb, I. H. (2017). A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature, 548(7668), 407–412. https://doi.org/10.1038/nature23480
  51. Lee, Z. Y., Lew, C. C. H., Ortiz-Reyes, A., Patel, J. J., Wong, Y. J., Loh, C. T. I., Martindale, R. G., & Heyland, D. K. (2023). Benefits and harm of probiotics and synbiotics in adult critically ill patients: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Clinical Nutrition, 42(4), 519–531. https://doi.org/10.1016/j.clnu.2023.01.019
  52. Sun, Y. C., Wang, C. Y., Wang, H. L., Yuan, Y., & Lu, J. H., Zhong, L. (2022). Probiotic in the prevention of ventilator-associated pneumonia in critically ill patients: Evidence from meta-analysis and trial sequential analysis of randomized clinical trials. BMC Pulmonary Medicine, 22(1), 168. https://doi.org/10.1186/s12890-022-01965-5
  53. Shimizu, K., Yamada, T., Ogura, H., Mohri, T., Kiguchi, T., Fujimi, S., Asahara, T., Yamada, T., Ojima, M., Ikeda, M., & Shimazu, T. (2018). Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: A randomized controlled trial. Critical Care, 22(1), 239. https://doi.org/10.1186/s13054-018-2167-x
  54. Stapleton, A. E., Au-Yeung, M., Hooton, T. M., Fredricks, D. N., Roberts, P. L., Czaja, C. A., Yarova-Yarovaya, Y., Fiedler, T., Cox, M., & Stamm, W. E. (2011). Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clinical Infectious Diseases, 52(10), 1212–1217. https://doi.org/10.1093/cid/cir183
  55. Lee, J. H., Kim, J., & Kim, G. Y. (2023). Synergistic effects of a probiotic culture extract and antimicrobial combinations against multidrug-resistant Acinetobacter baumannii. Medicina (Kaunas), 59(5), 947. https://doi.org/10.3390/medicina59050947
  56. Batoni, G., Catelli, E., Kaya, E., Pompilio, A., Bianchi, M., Ghelardi, E., Di Bonaventura, G., Esin, S., & Maisetta, G. (2023). Antibacterial and antibiofilm effects of Lactobacilli strains against clinical isolates of Pseudomonas aeruginosa under conditions relevant to cystic fibrosis. Antibiotics (Basel), 12(7), 1158. https://doi.org/10.3390/antibiotics12071158
  57. Dosler, S., & Gerceker, A. A. (2011). In vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. Chemotherapy, 57(6), 511–516. https://doi.org/10.1159/000335598
  58. FitzGerald, J., Patel, S., Eckenberger, J., Guillemard, E., Veiga, P., Schäfer, F., Walter, J., Claesson, M. J., & Derrien, M. (2022). Improved gut microbiome recovery following drug therapy is linked to abundance and replication of probiotic strains. Gut Microbes, 14(1), 2094664. https://doi.org/10.1080/19490976.2022.2094664
  59. Ture, Z., Güner, R., & Alp, E. (2022). Antimicrobial stewardship in the intensive care unit. Journal of Intensive Medicine, 3(3), 244–253. https://doi.org/10.1016/j.jointm.2022.10.001
  60. Mego, M., Koncekova, R., Mikuskova, E., Drgona, L., Ebringer, L., Demitrovicova, L., Nemova, I., Trupl, J., Mardiak, J., Koza, I., & Zajac, V. (2006). Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74: Phase II study. Supportive Care in Cancer, 14(3), 285–290. https://doi.org/10.1007/s00520-005-0891-7
  61. Persson, J. E., Viana, P., Persson, M., Relvas, J. H., & Danielski, L. G. (2024). Perioperative or postoperative probiotics reduce treatment-related complications in adult colorectal cancer patients undergoing surgery: A systematic review and meta-analysis. Journal of Gastrointestinal Cancer, 55(2), 740–748. https://doi.org/10.1007/s12029-024-01016-8
  62. Yang, Z., Zhang, S., Ying, L., Zhang, W., Chen, X., Liang, Y., Chen, R., Yao, K., Li, C., Yu, C., Jamilian, P., Zarezadeh, M., Kord-Varkaneh, H., Wang, J., & Li, H. (2025). The effect of probiotics supplementation on cancer-treatment complications: A critical umbrella review of interventional meta-analyses. Critical Reviews in Food Science and Nutrition, 65(19), 3702–3727. https://doi.org/10.1080/10408398.2024.2372880
  63. Alsuwaylihi, A. S., & McCullough, F. (2023). The safety and efficacy of probiotic supplementation for critically ill adult patients: A systematic review and meta-analysis. Nutrition Reviews, 81(3), 322–332. https://doi.org/10.1093/nutrit/nuac059
  64. Jackson, S. A., Schoeni, J. L., Vegge, C., Pane, M., Stahl, B., Bradley, M., Goldman, V. S., Burguière, P., Atwater, J. B., & Sanders, M. E. (2019). Improving end-user trust in the quality of commercial probiotic products. Frontiers in Microbiology, 10, 739. https://doi.org/10.3389/fmicb.2019.00739
  65. Latif, A., Shehzad, A., Niazi, S., Zahid, A., Ashraf, W., Iqbal, M. W., Rehman, A., Riaz, T., Aadil, R. M., Khan, I. M., Özogul, F., Rocha, J. M., Esatbeyoglu, T., & Korma, S. A. (2023). Probiotics: Mechanism of action, health benefits, and their application in food industries. Frontiers in Microbiology, 14, 1216674. https://doi.org/10.3389/fmicb.2023.1216674
  66. Lanza, V. F., Baquero, F., Martínez, J. L., Ramos-Ruíz, R., González-Zorn, B., Andremont, A., Sánchez-Valenzuela, A., Ehrlich, S. D., Kennedy, S., Ruppé, E., van Schaik, W., Willems, R. J., de la Cruz, F., & Coque, T. M. (2018). In-depth resistome analysis by targeted metagenomics. Microbiome, 6(1), 11. https://doi.org/10.1186/s40168-017-0387-y
  67. Doron, S., & Snydman, D. R. (2015). Risk and safety of probiotics. Clinical Infectious Diseases, 60(Suppl 2), S129–S134. https://doi.org/10.1093/cid/civ085
  68. Didari, T., Solki, S., Mozaffari, S., Nikfar, S., & Abdollahi, M. (2014). A systematic review of the safety of probiotics. Expert Opinion on Drug Safety, 13(2), 227–239. https://doi.org/10.1517/14740338.2014.872627
  69. Kiehn, T. E. (1989). Bacteremia and fungemia in the immunocompromised patient. European Journal of Clinical Microbiology & Infectious Diseases, 8(9), 832–837. https://doi.org/10.1007/BF02185856
  70. Yelin, I., Flett, K. B., Merakou, C., Mehrotra, P., Stam, J., Snesrud, E., Hinkle, M., Lesho, E., McGann, P., McAdam, A. J., Sandora, T. J., Kishony, R., & Priebe, G. P. (2019). Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nature Medicine, 25(11), 1728–1732. https://doi.org/10.1038/s41591-019-0626-9
  71. Wanyama, H., Akhtar, T. S., & Abbas, S. (2025). Probiotic use reduces the incidence of antibiotic-associated diarrhea among adult patients: A meta-analysis. Przegląd Gastroenterologiczny, 20(1), 5–16. https://doi.org/10.5114/pg.2025.148486
  72. Sanders, M. E., Akkermans, L. M., Haller, D., Hammerman, C., Heimbach, J., Hörmannsperger, G., Huys, G., Levy, D. D., Lutgendorff, F., Mack, D., Phothirath, P., Solano-Aguilar, G., & Vaughan, E. (2010). Safety assessment of probiotics for human use. Gut Microbes, 1(3), 164–185. https://doi.org/10.4161/gmic.1.3.12127
  73. Lamberte, L. E., & van Schaik, W. (2022). Antibiotic resistance in the commensal human gut microbiota. Current Opinion in Microbiology, 68, 102150. https://doi.org/10.1016/j.mib.2022.102150
  74. Zavišić, G., Popović, M., Stojkov, S., Medić, D., Gusman, V., Jovanović Lješković, N., & Jovanović Galović, A. (2023). Antibiotic resistance and probiotics: Knowledge gaps, market overview, and preliminary screening. Antibiotics (Basel), 12(8), 1281. https://doi.org/10.3390/antibiotics12081281
  75. Shahali, A., Soltani, R., & Akbari, V. (2023). Probiotic Lactobacillus and the potential risk of spreading antibiotic resistance: A systematic review. Research in Pharmaceutical Sciences, 18(5), 468–477. https://doi.org/10.4103/1735-5362.383703
  76. EFSA Panel on Biological Hazards (BIOHAZ), Koutsoumanis, K., Allende, A., Alvarez-Ordóñez, A., Bolton, D., Bover-Cid, S., Chemaly, M., De Cesare, A., Hilbert, F., Lindqvist, R., Nauta, M., Nonno, R., Peixe, L., Ru, G., Simmons, M., Skandamis, P., Suffredini, E., Cocconcelli, P. S., Fernández Escámez, P. S., … Herman, L. (2023). Update of the list of qualified presumption of safety (QPS) recommended microbiological agents intentionally added to food or feed as notified to EFSA 18: Suitability of taxonomic units notified to EFSA until March 2023. EFSA Journal, 21(7), e08092. https://doi.org/10.2903/j.efsa.2023.8092
  77. Cordaillat-Simmons, M., Rouanet, A., & Pot, B. (2020). Live biotherapeutic products: The importance of a defined regulatory framework. Experimental & Molecular Medicine, 52(9), 1397–1406. https://doi.org/10.1038/s12276-020-0437-6
  78. Garg, V., Velumani, D., Lin, Y. C., & Haye, A. (2024). A comprehensive review of probiotic claims regulations: Updates from Asia-Pacific, United States, and Europe. PharmaNutrition, 30, 100423. https://doi.org/10.1016/j.phanu.2024.100423
  79. Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Canani, R. B., Flint, H. J., Salminen, S., Calder, P. C., & Sanders, M. E. (2014). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506–514. https://doi.org/10.1038/nrgastro.2014.66
  80. Ghelardi, E., Mazzantini, D., Celandroni, F., Calvigioni, M., Panattoni, A., Lupetti, A., Bois De Fer, B., & Perez, M. (2023). Analysis of the microbial content of probiotic products commercialized worldwide and survivability in conditions mimicking the human gut environment. Frontiers in Microbiology, 14, 1127321. https://doi.org/10.3389/fmicb.2023.1127321
  81. Pane, M., Allesina, S., Amoruso, A., Nicola, S., Deidda, F., & Mogna, L. (2018). Flow cytometry: Evolution of microbiological methods for probiotics enumeration. Journal of Clinical Gastroenterology, 52(Suppl 1), S41–S45. https://doi.org/10.1097/MCG.0000000000001057
  82. Wang, Y., Tan, W., Li, X., Yang, G., Wang, Y., Liao, J., Lu, A., Zhang, G., Chen, K., Yang, L., & Li, W. (2025). A pharmacovigilance study on probiotic preparations based on the FDA Adverse Event Reporting System from 2005 to 2023. Frontiers in Cellular and Infection Microbiology, 15, 1455735. https://doi.org/10.3389/fcimb.2025.1455735
  83. European Medicines Agency (EMA). (2016). Guideline on good pharmacovigilance practices (GVP) – Product- or population-specific considerations II: Biological medicinal products. London: European Medicines Agency. Retrieved from https://www.ema.europa.eu
  84. International Council for Harmonisation (ICH). (2005). E2E pharmacovigilance planning. Geneva: ICH. Retrieved from https://www.ich.org
  85. Lange, L., Berg, G., Cernava, T., Champomier-Vergès, M.-C., Charles, T., Cocolin, L., … (2022). Microbiome ethics: Guiding principles for microbiome research, use, and knowledge management. Environmental Microbiome, 17, 50. https://doi.org/10.1186/s40793-022-00444-y
  86. Chidambaram, S., Maheswaran, Y., Chan, C., Hanna, L., Ashrafian, H., Markar, S. R., Sounderajah, V., Alverdy, J. C., & Darzi, A. (2022). Misinformation about the human gut microbiome in YouTube videos: Cross-sectional study. JMIR Formative Research, 6(5), e37546. https://doi.org/10.2196/37546
  87. Liu, Y.-Y., Hsu, C.-Y., Yang, Y.-C., Huang, C.-H., & Chen, C.-C. (2023). ProbioMinServer: An integrated platform for assessing the safety and functional properties of potential probiotic strains. Bioinformatics Advances, 3(1), vbad153. https://doi.org/10.1093/bioadv/vbad153
  88. Wang, L., He, Y., & Wu, Z. (2022). Design of a blockchain-enabled traceability system framework for food supply chains. Foods, 11(5), 744. https://doi.org/10.3390/foods11050744
  89. Rutter, J. W., Dekker, L., Owen, K. A., & Barnes, C. P. (2022). Microbiome engineering: Engineered live biotherapeutic products for treating human disease. Frontiers in Bioengineering and Biotechnology, 10, 1000873. https://doi.org/10.3389/fbioe.2022.1000873
  90. Salmikangas, P., Schuessler-Lenz, M., Ruiz, S., Celis, P., Reischl, I., Menezes-Ferreira, M., Flory, E., Renner, M., & Ferry, N. (2015). Marketing regulatory oversight of advanced therapy medicinal products (ATMPs) in Europe: The EMA/CAT perspective. Advances in Experimental Medicine and Biology, 871, 103–130. https://doi.org/10.1007/978-3-319-18618-4_6
  91. Marco, M. L., Sanders, M. E., Gänzle, M., Arrieta, M. C., Cotter, P. D., De Vuyst, L., Hill, C., Holzapfel, W., Lebeer, S., Merenstein, D., Reid, G., Wolfe, B. E., & Hutkins, R. (2021). The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods. Nature Reviews Gastroenterology & Hepatology, 18(3), 196–208. https://doi.org/10.1038/s41575-020-00390-5
  92. Codex Committee on Nutrition and Foods for Special Dietary Uses (CCNFSDU). (2024, July). Development of guidelines for probiotics (Agenda item 6.21): CX/NFSDU 24/44/6 Add.1. Rome: FAO/WHO Codex Alimentarius.
  93. Spacova, I., Binda, S., Ter Haar, J. A., Henoud, S., Legrain-Raspaud, S., Dekker, J., Espadaler-Mazo, J., Langella, P., Martín, R., Pane, M., & Ouwehand, A. C. (2023). Comparing technology and regulatory landscape of probiotics as food, dietary supplements and live biotherapeutics. Frontiers in Microbiology, 14, 1272754. https://doi.org/10.3389/fmicb.2023.1272754
  94. Zmora, N., Zilberman-Schapira, G., Suez, J., … (2018). Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell, 174(6), 1388–1405.e21. https://doi.org/10.1016/j.cell.2018.08.041
  95. McFarland, L. V., Evans, C. T., & Goldstein, E. J. C. (2018). Strain-specificity and disease-specificity of probiotic efficacy: A systematic review and meta-analysis. Frontiers in Medicine (Lausanne), 5, 124. https://doi.org/10.3389/fmed.2018.00124
  96. 96Wastyk, H. C., Perelman, D., Topf, M., Fragiadakis, G. K., Robinson, J. L., Sonnenburg, J. L., Gardner, C. D., & Sonnenburg, E. D. (2023). Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet. Gut Microbes, 15(1), 2178794. https://doi.org/10.1080/19490976.2023.2178794
  97. Maldonado-Gómez, M. X., Martínez, I., Bottacini, F., O’Callaghan, A., Ventura, M., van Sinderen, D., Hillmann, B., Vangay, P., Knights, D., Hutkins, R. W., & Walter, J. (2016). Stable engraftment of Bifidobacterium longum AH1206 in the human gut depends on individualized features of the resident microbiome. Cell Host & Microbe, 20(4), 515–526. https://doi.org/10.1016/j.chom.2016.09.001
  98. Abot, A., Brochot, A., Pomié, N., Astre, G., Druart, C., de Vos, W. M., Knauf, C., & Cani, P. D. (2023). Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release. Heliyon, 9(7), e18196. https://doi.org/10.1016/j.heliyon.2023.e18196
  99. Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J. J., Blugeon, S., Bridonneau, C., Furet, J. P., Corthier, G., Grangette, C., Vasquez, N., Pochart, P., Trugnan, G., Thomas, G., Blottière, H. M., Doré, J., Marteau, P., Seksik, P., & Langella, P. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences of the United States of America, 105(43), 16731–16736. https://doi.org/10.1073/pnas.0804812105
  100. Kunishima, H., Ishibashi, N., Wada, K., Oka, K., Takahashi, M., Yamasaki, Y., Aoyagi, T., Takemura, H., Kitagawa, M., & Kaku, M. (2019). The effect of gut microbiota and probiotic organisms on the properties of extended-spectrum beta-lactamase producing and carbapenem-resistant Enterobacteriaceae including growth, beta-lactamase activity and gene transmissibility. Journal of Infection and Chemotherapy, 25(11), 894–900. https://doi.org/10.1016/j.jiac.2019.04.021
  101. Hayashi, A., Nagao-Kitamoto, H., Kitamoto, S., Kim, C. H., & Kamada, N. (2021). The butyrate-producing bacterium Clostridium butyricum suppresses Clostridioides difficile infection via neutrophil- and antimicrobial cytokine-dependent but GPR43/109a-independent mechanisms. Journal of Immunology, 206(7), 1576–1585. https://doi.org/10.4049/jimmunol.2000353
  102. Rottinghaus, A. G., Ferreiro, A., Fishbein, S. R. S., Dantas, G., & Moon, T. S. (2022). Genetically stable CRISPR-based kill switches for engineered microbes. Nature Communications, 13(1), 672. https://doi.org/10.1038/s41467-022-28163-5
  103. Salminen, S., Collado, M. C., Endo, A., Hill, C., Lebeer, S., Quigley, E. M. M., Sanders, M. E., Shamir, R., Swann, J. R., Szajewska, H., & Vinderola, G. (2021). The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology, 18(9), 649–667. https://doi.org/10.1038/s41575-021-00440-6
  104. Jhong, J. H., Tsai, W. H., Yang, L. C., Chou, C. H., Lee, T. Y., Yeh, Y. T., Huang, C. H., & Luo, Y. H. (2022). Heat-killed Lacticaseibacillus paracasei GMNL-653 exerts antiosteoporotic effects by restoring the gut microbiota dysbiosis in ovariectomized mice. Frontiers in Nutrition, 9, 804210. https://doi.org/10.3389/fnut.2022.804210
  105. Davido, B., Merrick, B., Kuijper, E., Benech, N., Biehl, L. M., & Corcione, S. (2025). How can the gut microbiome be targeted to fight multidrug-resistant organisms? The Lancet Microbe, 6(8), 101063. https://doi.org/10.1016/j.lanmic.2024.101063
  106. Collignon, P. J., & McEwen, S. A. (2019). One Health—its importance in helping to better control antimicrobial resistance. Tropical Medicine and Infectious Disease, 4(1), 22. https://doi.org/10.3390/tropicalmed4010022
  107. Bermudez-Brito, M., Plaza-Díaz, J., Muñoz-Quezada, S., Gómez-Llorente, C., & Gil, A. (2012). Probiotic mechanisms of action. Annals of Nutrition and Metabolism, 61(2), 160–174. https://doi.org/10.1159/000342079
  108. Blaabjerg, S., Artzi, D. M., & Aabenhus, R. (2017). Probiotics for the prevention of antibiotic-associated diarrhea in outpatients: A systematic review and meta-analysis. Antibiotics (Basel), 6(4), 21. https://doi.org/10.3390/antibiotics6040021
  109. Ji, J., Jin, W., Liu, S. J., Jiao, Z., & Li, X. (2023). Probiotics, prebiotics, and postbiotics in health and disease. MedComm (2020), 4(6), e420. https://doi.org/10.1002/mco2.420
  110. Alam, S. T., Rahman, M. S., & Karmakar, S., … (2025). Mechanisms of action and health benefits of probiotics: A comprehensive review. Exploration of Digestive Diseases, 2(2), 1008129.
  111. Pitashny, M., Kesten, I., Shlon, D., Hur, D. B., & Bar-Yoseph, H. (2025). The future of microbiome therapeutics. Drugs, 85(2), 117–125. https://doi.org/10.1007/s40265-024-02107-3