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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/14/7/634 |
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| Summary: | 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. |
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| ISSN: | 2079-6382 |