The gut microbiome is closely connected to human health and well-being in many ways. While many microbes in the gut perform beneficial and essential tasks, others can pose a threat, like bacteria that secrete toxic molecules, for example. Scientists have begun to decipher some of those complex links, and we may one day be able to prevent or treat disease by modifying the microbiome.
Recent work has revealed more about how microbes in the gut may increase the risk of Alzheimer's disease. Previous research has shown that several types of Gram-negative bacteria release glycolipids such as lipopolysaccharide (LPS), which can cause neuroinflammation and disrupt immune signaling. While it has been difficult to connect specific microbes or their relative levels to certain neurological disorders, LPS is known as a neurotoxin that can drive disruptive, pro-inflammatory signaling.
Researchers have now shown how the BF-LPS neurotoxin, made by Gram-negative bacteria called Bacteroides fragilis, may lead to dementia. They also suggested there is an easy way to prevent that from happening. The findings have been reported in Frontiers in Neurology.
"LPSs in general are probably the most potent microbial-derived pro-inflammatory neurotoxic glycolipids known," noted senior study author Dr. Walter J. Lukiw of Louisiana State University. "Many laboratories, including our own, have detected different forms of LPS within neurons of the Alzheimer's disease-affected human brain."
This study has compiled data from mouse and human studies, as well as experiments on cells in culture to reveal how LPS triggers neuroinflammation. When gut microbes produce BF-LPS, it can leak out of the gut and travel through the circulatory system to the brain. BF-LPS is able to cross the blood brain barrier, and it triggers the NF-kB pathway as well as a microRNA molecule called miRNA-30b, which also impacts NF-kB.
In cells in culture, this microRNA led to a reduction of NF-L expression. Low NF-L levels have been linked to atrophy in the cytoskeleton of neurons, and a disruption of synaptic organization. Loss of NF-L eventually caused death in neurons.
However, the study authors also noted that the intake of proper levels of dietary fiber may prevent this effect. While Bacteroides fragilis that generate the neurotoxin BF-LPS are typically found in abundance in the gut microbiome, dietary fiber can control the microbes, and their toxin. The average American consumes around 12 grams of fiber every day, while the USDA-recommended levels are around 25 grams for women and 38 grams for men.
"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 explained.