Study links gut bacteria infection to Alzheimer's disease progression

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."

Ravinder Nagpal, assistant professor in the FSU College of Education, Health, and Human Sciences and 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.

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.

Source:
Journal reference:

Park, G., et al. (2024). An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice. The Journal of Infectious Diseases. doi.org/10.1093/infdis/jiae165.

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