Gut-based neurotoxin triggers inflammation associated with Alzheimer's disease

A neurotoxin derived from bacteria in the gastrointestinal tract has been identified as a major contributor to Alzheimer’s disease, researchers reported in Frontiers in Neurology.

The microbial-generated neurotoxin lipopolysaccharide (LPS) is derived from the gut-based, gram-negative bacteria Bacteroides fragilis and creates a pro-inflammatory neurotoxin called BF-LPS, Walter J. Lukiw, MS, PhD, the Bollinger Professor of Alzheimer’s disease and professor of neuroscience, neurology and ophthalmology at Louisiana State University, and colleagues reported.

“LPSs in general are probably the most potent microbial-derived pro-inflammatory neurotoxic glycolipids known,” Lukiw said in a university release. “Many laboratories, including our own, have detected different forms of LPS within neurons of the Alzheimer’s disease-affected human brain.”

According to Lukiw and colleagues, BF-LPS leaks out of the GI tract, crosses the blood-brain barrier through the circulatory system and penetrates areas of the brain. BF-LPS then induces inflammation in brain cells and inhibits neuron-specific neurofilament light, a protein that encourages cell integrity, which can lead to neuronal cell atrophy and cell death. This type of degeneration is observed in AD-affected neurons.

The researchers reported that the AD-stimulating pathway described is active throughout life and that the neurotoxic BF-LPS is a natural byproduct of microbial metabolism. The gram-negative culprit Bacteroides fragilis can be regulated by increased dietary fiber intake.

“Put another way, dietary-based approaches to balance the microorganisms in the microbiome may be an attractive means to modify the abundance, speciation and complexity of enterotoxigenic forms of AD-relevant microbes and their potential for the pathological discharge of highly neurotoxic microbial-derived secretions that include BF-LPS and other forms of LPS,” Lukiw said in the release.

Reference:

LSU Health New Orleans discovers major contributor to Alzheimer's disease. https://www.lsuhsc.edu/newsroom/LSU%20Health%20New%20Orleans%20Discovers%20Major%20Contributor%20to%20Alzheimer%E2%80%99s%20Disease.html. Published Aug. 9, 2022. Accessed Aug. 9, 2022.