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Published on: November 17, 2018
Melatonin Confers Protection Against Multidrug-Resistant Bacterial Infections in Aged Mice Via Microbiota-Derived
Wenjiao Xu1,2, Jiaqi Bo1,3, Liyan Jia4
1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China.
Abstract:
Aging is associated with increased susceptibility to bacterial infections, particularly multidrug-resistant (MDR) strains, which often result in antibiotic treatment failure and high mortality rates in the elderly. However, effective preventive and therapeutic strategies remain limited. Herein, we showed that aged mice exhibited higher susceptibility to colistin-resistant Salmonella enterica serotype Typhimurium and methicillin-resistant Staphylococcus aureus compared to young mice. Notably, pre-supplementation with melatonin, a hormone markedly reduced in the aging gut, effectively restricted MDR bacterial infections in aged mice by enhancing microbial colonization resistance. Mechanistically, melatonin-induced alterations in the gut microbiota, particularly the enrichment of butyrate-producing bacteria including Faecalibaculum, Muribaculaceae, and Ruminococcus, played a pivotal role in enhancing resistance to pathogenic bacteria. Elevated gut butyrate levels following melatonin pre-supplementation not only preserved intestinal barrier integrity and mitigated inflammaging, but also directly inhibited pathogenic bacterial growth by disrupting intracellular pH homeostasis, leading to proton motive force dissipation and metabolic disturbances. These findings underscore melatonin and its metabolite, butyrate, as promising candidates for the prevention of MDR bacterial infections in the aging population.
Insights
Melatonin supplementation enhances gut microbiota in aging mice, boosting resistance to multidrug-resistant (MDR) bacterial infections. This strategy combats infections and improves health outcomes in the elderly.
Area of Science:
- Microbiology
- Immunology
- Gerontology
Background:
- Aging increases susceptibility to multidrug-resistant (MDR) bacterial infections, leading to treatment failure and mortality in the elderly.
- Current preventive and therapeutic strategies for these infections in older adults are limited.
Purpose of the Study:
- To investigate the efficacy of melatonin pre-supplementation in enhancing resistance to MDR bacterial infections in aged mice.
- To elucidate the underlying mechanisms of melatonin's protective effects on the aging gut microbiota and immune response.
Main Methods:
- Aged and young mice were infected with colistin-resistant Salmonella Typhimurium and methicillin-resistant Staphylococcus aureus.
- Melatonin was administered as a pre-supplementation strategy to aged mice.
- Gut microbiota composition, short-chain fatty acid levels (especially butyrate), intestinal barrier integrity, and inflammaging markers were analyzed.
- Direct effects of butyrate on pathogenic bacteria were assessed.
Main Results:
- Aged mice showed higher susceptibility to MDR bacterial infections compared to young mice.
- Melatonin pre-supplementation significantly restricted MDR bacterial infections in aged mice by enhancing colonization resistance.
- Melatonin enriched beneficial butyrate-producing bacteria (e.g., Faecalibaculum, Muribaculaceae, Ruminococcus) and increased gut butyrate levels.
- Elevated butyrate preserved intestinal barrier integrity, mitigated inflammaging, and directly inhibited pathogenic bacterial growth via pH homeostasis disruption.
Conclusions:
- Melatonin effectively enhances gut microbial defense against MDR bacterial infections in aged mice.
- Melatonin and its metabolite butyrate show promise as preventive strategies against MDR infections in the aging population.
- Targeting gut microbiota and metabolic pathways offers a novel approach to combat age-related infectious disease susceptibility.
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