Scientists discover massive new contributor to Alzheimer’s disease

Research led by Drs. Yuhai Zhao and Walter J Lukiw at the LSU Health New Orleans Neuroscience Center has uncovered a pathway that begins in your gut and ends with a potent pro-inflammatory toxin in your brain cells, contributing to the development of Alzheimer’s disease (AD). The findings, published in Frontiers in Neurology, also suggest a simple preventive measure.

The researchers identified a molecule containing a highly potent neurotoxin (lipopolysaccharide or LPS) produced by the Gram-negative bacteria Bacteroides fragilis in the human gastrointestinal (GI) tract. This neurotoxin, known as BF-LPS, poses significant risks.

“LPSs are probably the most potent microbial-derived pro-inflammatory neurotoxic glycolipids known,” says Dr. Lukiw. “Many laboratories, including ours, have detected different forms of LPS within neurons of Alzheimer’s disease-affected brains.”

In this study, the team describes how BF-LPS travels from your gut to your brain and its effects once there. BF-LPS leaks from the GI tract, crosses the blood-brain barrier via the circulatory system, and reaches brain compartments.

Once in the brain, it increases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L), a protein crucial for cell integrity.

A lack of this protein leads to progressive neuronal cell atrophy and, ultimately, cell death, as seen in AD-affected neurons. The researchers also found that a sufficient intake of dietary fiber can prevent this process.

The newly described pathological pathway has three notable features. First, the AD-stimulating pathway starts within your GI-tract microbiome and remains active throughout your life. Second, the highly potent neurotoxin BF-LPS is a natural by-product of microbial metabolism in the GI tract. Third, the abundance of Bacteroides fragilis in the microbiome, which produces BF-LPS, can be controlled by dietary fiber intake.

“Dietary-based approaches to balance 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,” explains Lukiw.

The researchers believe that a better understanding of the interaction between the GI tract-Central Nervous System axis, the GI-tract microbiome, and Alzheimer’s disease could lead to new diagnostic and therapeutic strategies for managing Alzheimer’s and other age-related neurodegenerative disorders.

Americans typically consume 10-15 grams of fiber daily. The USDA recommends women up to age 50 consume 25 grams daily, and men 38 grams. Over age 50, women should consume 21 grams and men 30 grams daily.

According to the National Institutes of Health, Alzheimer’s disease is the most common diagnosis for patients with dementia and the sixth leading cause of death in the United States. Experts estimate that 5.8 million Americans aged 65 and older have Alzheimer’s disease, with the number projected to rise to 13.8 million by 2050.

LSU Health New Orleans co-authors included Drs. Vivian Jaber and Nathan Sharfman. Aileen Pogue from Alchem Biotech Research in Toronto, Canada, was also a co-author.

The research received support from LSU Health New Orleans, the Brown Foundation, the Joe and Dorothy Dorsett Innovation in Science Health Aging Award, and the National Institutes on Aging of the National Institutes of Health.

According to the Cleveland Clinic, the top 5 largest sources of dietary fiber in the U.S. diet include a variety of fruits, vegetables, grains, nuts, seeds, and legumes. Here is a detailed list:

These sources contribute significantly to the fiber intake in the American diet, promoting digestive health and reducing the risk of various diseases. Most Americans consume only about 15 grams of fiber daily, which is below the recommended intake. Incorporating these fiber-rich foods can help bridge this gap.

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