How Opportunistic Bacteria Trigger Neuroinflammation via the Gut-Brain Axis
New findings on the link between bacterial infection and Alzheimer’s disease highlight the importance of gut health.
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The gut microbiome is considered one of the key elements contributing to overall health. An abnormal gut microbiome, characterized by unusually high carriage of specific bacteria, has been linked to mild cognitive impairment and prodromal Alzheimer’s disease.
One opportunistic pathogen is Klebsiella pneumoniae (K. pneumoniae) – a common bacteria infamous for hospital-acquired infections and sepsis. Now, researchers at Florida State University have described, in mice, how K. pneumoniae can migrate from the gut into the bloodstream and eventually into the brain, resulting in symptoms often observed in Alzheimer's patients.
The study, published in The Journal of Infectious Diseases, is the first to show a direct correlation between K. pneumoniae infection and Alzheimer’s pathology. The findings emphasize the potential risk hospital-acquired infections may pose in neurodegenerative disease development.
Gut disruption makes patients vulnerable to infection
Hospital-acquired infections are one of the most common complications of hospital care and are among the top 10 leading causes of death in the United States. A major concern with these infections is their overlap with antibiotic resistance, likely due to the widespread use of antibacterial drugs.
Antibiotics are generally effective at targeting harmful bacteria, but they can disrupt the balance of beneficial and commensal bacteria in the gut. This gut microbial disruption and depleted diversity create an environment conducive to the overgrowth of certain antibiotic-resistant pathogens, such as K. pneumoniae.
“Normally, K. pneumoniae is a subdominant part of the gut microbiome and remains constrained and harmless in healthy individuals; however, when antibiotics disturb this balance, it can proliferate and pose significant health risks, particularly if it spreads to other parts of the body,” Dr. Ravinder Nagpal, assistant professor at Florida State University and director of the Gut Biome Lab, told Technology Networks.
“Our research indicates that when K. pneumoniae overgrows, it can migrate from the gut to the brain, triggering severe neuroinflammation. This inflammatory response is particularly concerning in Alzheimer's disease models, as it may exacerbate cognitive decline and contribute to the disease's progression.”
Researchers used a preclinical mouse model to explore whether, and how, K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis. Young mice were infected with K. pneumoniae isolated from the human gut and then treated with an antibiotic to induce gut dysbiosis.
“In our infected mice, we observed several neurocognitive impairments, including impaired motor function, compromised neuromuscular function and heightened anxiety-like symptoms,” explained Nagpal. “These impairments closely mimic symptoms observed in human neurodegenerative diseases like Alzheimer's, where patients often experience anxiety, difficulties with coordination and movement and challenges in performing daily activities due to neuromuscular deficits.”
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Subscribe for FREEAlongside neurobehavioral impairments, the researchers found elevated levels of tau protein in the brains of infected mice. Tau protein aggregation is a hallmark of Alzheimer's disease and is associated with neurodegeneration and cognitive decline. “Our findings suggest that bacterial infections, such as those caused by infectious agents like K. pneumoniae, can trigger neuroinflammatory processes that lead to tau phosphorylation and accumulation,” said Nagpal.
Taken together, these findings indicate that microbial factors might contribute to the pathophysiology of neurodegenerative diseases. These findings have strong clinical significance and Nagpal shares how they highlight “the importance of gut health and the potential for targeting bacterial infections as a therapeutic strategy to mitigate neurodegeneration and improve cognitive outcomes.”
Using dietary interventions to prevent bacterial invasion
Since antibiotics can disrupt the balance of beneficial bacteria in the gut, implementing interventions to restore the gut microbiome in patients taking antibiotics could be key to reducing the risk of hospital-acquired infections. “It is essential to incorporate pro-, pre- and postbiotic treatments or tailored dietary patterns to facilitate the recovery of a healthy microbial community,” states Nagpal.
He concludes, “by prioritizing gut health, we can reduce the risk of opportunistic pathogen overgrowth, such as K. pneumoniae, thereby enhancing patient outcomes and preventing complications related to neuroinflammation and neurodegeneration.”
Reference: Park G, Kadyan S, Hochuli N, et al. An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice. J Infect Dis. 2024. doi: 10.1093/infdis/jiae165
About the interviewee:
Dr. Ravinder Nagpal is an assistant professor at Florida State University and the director of the Gut Biome Lab. Nagpal holds a PhD in dairy microbiology from the National Dairy Research Institute in India. His research focuses on understanding the role of the gut microbiome in host aging-associated intestinal and neurocognitive health.
