Summary: Researchers have discovered that the gut bacteria Klebsiella pneumoniae can migrate to the brain, leading to inflammation and cognitive decline that mimic Alzheimer’s symptoms. The study suggests that hospital-acquired infections combined with disrupted gut microbiomes may increase the risk of developing neurodegenerative diseases.
Using a mouse model, scientists found that antibiotic exposure can cause microbiome imbalances, allowing K. pneumoniae to reach the brain. This study opens new avenues for preventing Alzheimer’s by managing infections and gut health.
Key Facts:
- Klebsiella pneumoniae can migrate from the gut to the brain, triggering neuroinflammation.
- Disrupted gut microbiomes after antibiotic use may contribute to Alzheimer’s risk.
- The study emphasizes the role of hospital-acquired infections in neurodegenerative diseases.
Source: FSU
A groundbreaking study by researchers at Florida State University’s Gut Biome Lab has revealed a potential link between an infection caused by gut bacteria and the progression of Alzheimer’s disease.
The research found that the bacteria Klebsiella pneumoniae — a common bacteria notorious for causing hospital-acquired infections — can migrate from the gut into the bloodstream and eventually into the brain.
This bacterial invasion may lead to increased inflammation in the brain and impair cognitive functions, mimicking symptoms seen in Alzheimer’s patients.
The work was published in The Journal of Infectious Diseases.
“Hospitalizations and ICU stays, combined with antibiotic exposure, may lead to a further decline in microbiome diversity that leaves older adults at high risk not only for digestive issues but also for extra-intestinal pathologies such as neurodegenerative disorders through a dysregulation of the gut-brain axis,” said Ravinder Nagpal, an assistant professor in the FSU College of Education, Health, and Human Sciences and the director of the Gut Biome Lab.
The study is the first to show a direct correlation between K. pneumoniae infection and Alzheimer’s pathology, fueling the emerging field that investigates how infectious agents may trigger or aggravate Alzheimer’s disease.
It also paves the way for future research into how to treat harmful infectious agents in vulnerable populations such as the elderly or those recovering from sepsis.
The research suggests that when antibiotics disrupt the gut, it can lead to issues not just in the gut but also in the brain. Using a preclinical mouse model, researchers showed that antibiotic exposure depletes gut bacterial diversity and causes microbiome imbalance, which promotes the proliferation of K. pneumoniae by creating a favorable niche.
When this happens, K. pneumoniae can move from the gut into the bloodstream by passing through the gut lining and eventually reach the brain, triggering neuroinflammation and neurocognitive impairment.
The findings emphasize the potential risk hospital-acquired infections like K. pneumoniae may pose in the development of neurodegenerative diseases.
“Hospital-acquired and septic infections are one of the risk factors that may increase the predispositions to future neuroinflammatory and neurocognitive impairments, especially in older adults,” Nagpal said.
The study highlights the need for innovative therapeutic approaches to combat the rising prevalence of Alzheimer’s disease, in addition to existing amyloid and tau protein therapies. Further research could provide insight into preventive strategies aimed at managing hospital-acquired pathogens and preserving cognitive health in aging populations.
Funding: The research was funded by the Infectious Diseases Society of America and the Florida Department of Health.
The paper was co-authored by graduate researchers Ian Park, Saurabh Kadyan, and Nathaniel Hochuli from the FSU College of Education, Health, and Human Sciences. Additional collaborators included Hazel K. Stiebeling Professor Gloria Salazar; Associate Professor of psychology and neuroscience Aaron Wilber; University of Florida researchers Orlando Laitano, Paramita Chakrabarty, and Philip A. Efron; and Wake Forest University School of Medicine Associate Professor M. Ammar Zafar.
About this Alzheimer’s disease and microbiome research news
Author: Bill Wellock
Source: FSU
Contact: Bill Wellock – FSU
Image: The image is credited to Neuroscience News
Original Research: Open access.
“An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice” by Ravinder Nagpal et al. Journal of Infectious Diseases
Abstract
An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice
Background
Klebsiella pneumoniae is infamous for hospital-acquired infections and sepsis, which have also been linked to Alzheimer disease (AD)-related neuroinflammatory and neurodegenerative impairment. However, its causative and mechanistic role in AD pathology remains unstudied.
Methods
A preclinical model of K. pneumoniae enteric infection and colonization is developed in an AD model (3xTg-AD mice) to investigate whether and how K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis.
Results
K. pneumoniae, particularly under antibiotic-induced dysbiosis, was able to translocate from the gut to the bloodstream by penetrating the gut epithelial barrier. Subsequently, K. pneumoniae infiltrated the brain by breaching the blood-brain barrier. Significant neuroinflammatory phenotype was observed in mice with K. pneumoniae brain infection. K. pneumoniae-infected mice also exhibited impaired neurobehavioral function and elevated total tau levels in the brain.
Metagenomic analyses revealed an inverse correlation of K. pneumoniae with gut biome diversity and commensal bacteria, highlighting how antibiotic-induced dysbiosis triggers an enteroseptic “pathobiome” signature implicated in gut-brain perturbations.
Conclusions
The findings demonstrate how infectious agents following hospital-acquired infections and consequent antibiotic regimen may induce gut dysbiosis and pathobiome and increase the risk of sepsis, thereby increasing the predisposition to neuroinflammatory and neurobehavioral impairments via breaching the gut-blood-brain barrier.
