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Updated: Aug 15, 2025
Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
Melatonin Is Neuroprotective in Escherichia coli Meningitis Depending on Intestinal Microbiota
Dong Zhang1,2,3, Shu Xu1,2,3, Hucong Wu1,2,3
1College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Abstract:
Avian meningitis Escherichia coli (E. coli) can cause acute bacterial meningitis which threatens poultry health, causes great economic losses in the poultry industry, and has recently been speculated as a potential zoonotic pathogen. Melatonin can counteract bacterial meningitis-induced disruption of the blood-brain barrier (BBB), neuroinflammation, and reduce mortality. There are increasing data showing that melatonin's beneficial effects on bacterial meningitis are associated with intestinal microbiota. In this study, our data showed that melatonin alleviated neurological symptoms, enhanced survival rate, protected the integrity of the BBB, reduced the bacterial load in various tissues and blood, and inhibited inflammation and neutrophil infiltration of brain tissue in an APEC TW-XM-meningitis mice model. The results of 16S rRNA showed that melatonin pretreatment significantly maintained the composition of intestinal microbiota in APEC-meningitis mice. The abundance and diversity of intestinal microbiota were disturbed in APEC TW-XM-meningitis mice, with a decreased ratio of Firmicutes to Bacteroides and an increased the abundance of Proteobacteria. Melatonin pretreatment could significantly improve the composition and abundance of harmful bacteria and alleviate the decreased abundance of beneficial bacteria. Importantly, melatonin failed to affect the meningitis neurologic symptoms caused by APEC TW-XM infection in antibiotic-pretreated mice. In conclusion, the results suggest that melatonin can effectively prevent meningitis induced by APEC TW-XM infection in mice, depending on the intestinal microbiota. This finding is helpful to further explore the specific target mechanism of melatonin-mediated intestinal microbiota in the prevention of and protection against Escherichia coli meningitis.
Insights
Melatonin effectively prevents avian pathogenic Escherichia coli (E. coli) meningitis in mice by modulating the gut microbiota. Its protective effects depend on a healthy intestinal microbial community, highlighting a novel therapeutic approach.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Avian pathogenic Escherichia coli (E. coli) causes bacterial meningitis, posing significant threats to poultry health and the economy.
- E. coli meningitis is also a potential zoonotic concern.
- Melatonin is known to counteract meningitis-induced effects like blood-brain barrier disruption and neuroinflammation.
Purpose of the Study:
- To investigate the protective role of melatonin against E. coli meningitis in a mouse model.
- To explore the association between melatonin's efficacy and the intestinal microbiota composition.
Main Methods:
- Establishment of an avian pathogenic E. coli (APEC) TW-XM meningitis mouse model.
- Administration of melatonin pretreatment.
- Analysis of intestinal microbiota using 16S rRNA sequencing.
- Assessment of neurological symptoms, survival rates, blood-brain barrier integrity, bacterial load, and inflammation.
Main Results:
- Melatonin treatment alleviated neurological symptoms, improved survival, protected the blood-brain barrier, and reduced bacterial load and brain inflammation in APEC-infected mice.
- APEC infection altered intestinal microbiota diversity, decreasing the Firmicutes/Bacteroides ratio and increasing Proteobacteria.
- Melatonin pretreatment restored beneficial bacteria and reduced harmful bacteria, maintaining intestinal microbiota homeostasis.
- Melatonin's protective effects were abolished in antibiotic-treated mice, indicating dependence on the intestinal microbiota.
Conclusions:
- Melatonin effectively prevents APEC-induced meningitis in mice, with its efficacy being dependent on the intestinal microbiota.
- These findings suggest melatonin's potential as a therapeutic agent for E. coli meningitis, mediated through gut microbiota modulation.
- Further research into the specific mechanisms of melatonin-mediated gut microbiota is warranted.
