Could some gut bacteria contribute to Alzheimer’s?

For this study, researchers used a mouse model of Alzheimer’s disease infected with K. pneumoniae.

During the study, scientists found that when the mice were exposed to antibiotics, the diversity of their gut bacteria depleted, causing a microbiome imbalance.

This then allowed K. pneumoniae to migrate from the gut into the bloodstream by passing through the gut lining.

From there, the bacteria traveled into the brain, causing neuroinflammation and neurocognitive impairment, both of which are known Alzheimer’s disease symptoms.

These findings, researchers say, emphasizes the possible risk hospital-acquired infections like K. pneumoniae might cause in the development of neurodegenerative diseases.

Ravinder Nagpal, PhD, an assistant professor in the College of Education, Health, and Human Sciences and the director of the Gut Biome Lab at Florida State University and one of the authors of this study, explained to Medical News Today that “K. pneumoniae is a type of gram-negative bacteria often found in very subdominant levels in the human gut, where it usually remains constrained and harmless in healthy people.“

“However,“ he added, “in certain situations — such as when antibiotics disrupt the microbiome diversity and gut’s balance of bacteria — K. pneumoniae, being antibiotic-resistant, can overgrow and cause problems, particularly if it spreads to other parts of the body.“

“Our research found that when K. pneumoniae overgrows, it can trigger severe inflammation by moving from the gut to the brain. In Alzheimer’s disease milieus, this added inflammation may worsen symptoms by dysregulating the blood-brain barrier (the protective layer surrounding the brain) and putting extra inflammatory stress on brain cells. Over time, these effects could potentially initiate or worsen Alzheimer’s disease, making K. pneumoniae a significant focus in research on how gut bacteria may impact brain health.”

– Ravinder Nagpal, PhD

The researchers believe their findings may also open the door to new therapies for Alzheimer’s disease.

“Our findings suggest that restoring balance in an imbalanced gut environment may offer a promising therapeutic approach for Alzheimer’s disease, with precision nutrition strategies and pro-, pre-, and postbiotic treatments as potential options to restore the depleted microbiome diversity,“ Nagpal told us.

MNT had the chance to speak with David Merrill, MD, PhD, geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, CA, about this study.

Merrill commented that this is an interesting animal model study showing us a mechanism underlying the gut-brain connection.

“Antibiotic treatment of gut illnesses can lead to unintended consequences that increase our risk of neurodegenerative diseases down the line,” he explained. “Understanding the cascade of events leading to neurodegenerative diseases may allow us to change the treatment approach to pathological bacterial infections of the gut.”

“Preventing the development of Alzheimer’s by treating gut problems differently may be possible,” Merrill added. “It’d be great to see interventions tried in these same animal models to then be translated into use in patients.”

MNT also spoke with Ashkan Farhadi, MD, a board-certified gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, about this study.

Farhadi, who was not involved in the research, commented that while the title of the study was intriguing, and there were interesting and positive aspects of the study, the substance of the study was not as comprehensive as it could have been.

“[The authors] are just making some statements that are really broad — much broader than the finding,” he suggested.

“[They] are claiming that the gut bacteria can get from here to there, while they only showed one possible gut bacteria in a setting of antibiotic got into the bloodstream, which is good, and we knew that. When a patient is exposed to antibiotics, you can get an infection because the gut barrier gets disrupted,” explained Farhadi.

“They also showed that when the blood gets infected, we thought the blood-brain barrier [was] going to protect the invasion of the bacteria to the brain, but that also was not true, as this bacteria passed that barrier as well and got into [the] brain,” he continued.

“We always knew that during sepsis or infection in the blood, we are having septic encephalopathy, which means the brain may not function properly during sepsis. But this shows that actually we are having encephalitis because of the infection — that’s not unheard of. It is very interesting that the authors put together a narrative that we already knew pieces and parcels of, but put it in a narrative that put everything in one perspective”

Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, also took the time to talk to MNT about this new research.

Segil said he thought it was strange that a study outlining a blood borne infection that travels to the brain and causes confusion does not use the words meningitis, encephalitis, or delirium.

“Any time someone gets an infection in their brain, outside their brain is called meningitis [and] inside of their brain is encephalitis,” he explained.

And all brain infections cause confusion, and most of the time, this confusion is reversible, and it’s called delirium. I’m surprised this whole article talks about people getting brain infections and being confused, but doesn’t have the word meningitis or delirium,” said Segil.

“This was a study [in] mice and to extrapolate any type of human behavioral conclusions based on mouse behavioral studies is challenging,” he cautioned. “You would have to do repeat studies between something the size of a mouse and something the size of a person.”

Finally, “the idea that an infection is going to cause dementia is not accepted,” he added. “Infections cause delirium. Delirium is the word we use for when people are infected and confused with an infection, and this article doesn’t acknowledge that we already have an understanding of how infections cause transient confusion.”