Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model
Background/Objectives<b>:</b> Alternative therapies for urinary tract infections (UTIs) have been explored, but their efficacy remains inconsistent. With rising antibiotic resistance, this study aimed to evaluate simplified postbiotic formulations derived from heat-killed probiotics for...
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MDPI AG
2025-06-01
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| author | Bo-Yuan Chen Zhen-Shu Liu Yu-Syuan Lin Hsiao Chin Lin Po-Wen Chen |
| author_facet | Bo-Yuan Chen Zhen-Shu Liu Yu-Syuan Lin Hsiao Chin Lin Po-Wen Chen |
| author_sort | Bo-Yuan Chen |
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| description | Background/Objectives<b>:</b> Alternative therapies for urinary tract infections (UTIs) have been explored, but their efficacy remains inconsistent. With rising antibiotic resistance, this study aimed to evaluate simplified postbiotic formulations derived from heat-killed probiotics for long-term protection against primary and recurrent UTIs in a murine model. Methods: We compared a multi-strain (seven-strain) versus a single-strain postbiotic in preventing <i>Escherichia coli</i>-induced UTIs and recurrent polymicrobial UTIs, assessed protection persistence after treatment discontinuation, and established a novel sustained UTI model via intravesical co-inoculation of three uropathogens. Mice were allocated to three experimental groups: a placebo group (PBS), Postbiotic I group (a seven-strain heat-killed probiotic formulation), and Postbiotic II group (a single-strain heat-killed probiotic). After two weeks of treatment, mice were challenged with uropathogenic <i>E. coli</i> (UPEC) and treated for seven days. Following a 14-day washout and bacterial clearance, they were rechallenged with multidrug-resistant UPEC, <i>Klebsiella pneumoniae</i>, and <i>Staphylococcus pseudintermedius</i>. Results: Both postbiotics significantly accelerated bacterial clearance in primary UTIs (<i>p</i> < 0.05). In recurrent UTIs, placebo-treated mice exhibited persistent bacteriuria, while Postbiotic I maintained a significantly higher sterile urine rate (50–80%, <i>p</i> < 0.01) post-treatment. Histopathological analysis confirmed reduced bladder and kidney inflammation (<i>p</i> < 0.05) with Postbiotic I. Conclusions: These findings demonstrate the superior efficacy of Postbiotic I in mitigating UTIs, with sustained protection post-treatment, supporting its potential as a long-term, non-antibiotic strategy. Additionally, our reproducible chronic UTI model, achieved through the co-inoculation of three uropathogens, provides a valuable tool for future research on chronic UTI pathogenesis and treatment. |
| format | Article |
| id | doaj-art-e020ac78b3c74c2da667dd0a3d347130 |
| institution | DOAJ |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj-art-e020ac78b3c74c2da667dd0a3d3471302025-08-20T03:13:42ZengMDPI AGAntibiotics2079-63822025-06-0114763410.3390/antibiotics14070634Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine ModelBo-Yuan Chen0Zhen-Shu Liu1Yu-Syuan Lin2Hsiao Chin Lin3Po-Wen Chen4Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40249, TaiwanDepartment of Safety, Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 24301, TaiwanDepartment of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40249, TaiwanDepartment of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40249, TaiwanDepartment of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40249, TaiwanBackground/Objectives<b>:</b> Alternative therapies for urinary tract infections (UTIs) have been explored, but their efficacy remains inconsistent. With rising antibiotic resistance, this study aimed to evaluate simplified postbiotic formulations derived from heat-killed probiotics for long-term protection against primary and recurrent UTIs in a murine model. Methods: We compared a multi-strain (seven-strain) versus a single-strain postbiotic in preventing <i>Escherichia coli</i>-induced UTIs and recurrent polymicrobial UTIs, assessed protection persistence after treatment discontinuation, and established a novel sustained UTI model via intravesical co-inoculation of three uropathogens. Mice were allocated to three experimental groups: a placebo group (PBS), Postbiotic I group (a seven-strain heat-killed probiotic formulation), and Postbiotic II group (a single-strain heat-killed probiotic). After two weeks of treatment, mice were challenged with uropathogenic <i>E. coli</i> (UPEC) and treated for seven days. Following a 14-day washout and bacterial clearance, they were rechallenged with multidrug-resistant UPEC, <i>Klebsiella pneumoniae</i>, and <i>Staphylococcus pseudintermedius</i>. Results: Both postbiotics significantly accelerated bacterial clearance in primary UTIs (<i>p</i> < 0.05). In recurrent UTIs, placebo-treated mice exhibited persistent bacteriuria, while Postbiotic I maintained a significantly higher sterile urine rate (50–80%, <i>p</i> < 0.01) post-treatment. Histopathological analysis confirmed reduced bladder and kidney inflammation (<i>p</i> < 0.05) with Postbiotic I. Conclusions: These findings demonstrate the superior efficacy of Postbiotic I in mitigating UTIs, with sustained protection post-treatment, supporting its potential as a long-term, non-antibiotic strategy. Additionally, our reproducible chronic UTI model, achieved through the co-inoculation of three uropathogens, provides a valuable tool for future research on chronic UTI pathogenesis and treatment.https://www.mdpi.com/2079-6382/14/7/634uropathogenic <i>Escherichia coli</i>recurrent urinary tract infectionspostbioticheat-killed probioticmice modellactic acid bacteria |
| spellingShingle | Bo-Yuan Chen Zhen-Shu Liu Yu-Syuan Lin Hsiao Chin Lin Po-Wen Chen Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model Antibiotics uropathogenic <i>Escherichia coli</i> recurrent urinary tract infections postbiotic heat-killed probiotic mice model lactic acid bacteria |
| title | Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model |
| title_full | Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model |
| title_fullStr | Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model |
| title_full_unstemmed | Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model |
| title_short | Oral Administration of Heat-Killed Multi-Strain Probiotics Confers Durable Protection Against Antibiotic-Resistant Primary and Recurrent Urinary Tract Infections in a Murine Model |
| title_sort | oral administration of heat killed multi strain probiotics confers durable protection against antibiotic resistant primary and recurrent urinary tract infections in a murine model |
| topic | uropathogenic <i>Escherichia coli</i> recurrent urinary tract infections postbiotic heat-killed probiotic mice model lactic acid bacteria |
| url | https://www.mdpi.com/2079-6382/14/7/634 |
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