Author Archives: jpnd

Scientists have discovered for the first time a functional link between bacteria in the intestines and Parkinson’s disease (PD). The researchers show that changes in the composition of gut bacterial populations–or possibly gut bacteria themselves–are actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.

The work–which has profound implications for the treatment of PD–appears in Cell.

PD affects up to 10 million worldwide, making it the second most common neurodegenerative disease. Characteristic features of PD include symptoms such as tremors and difficulty walking, aggregation of a protein called alpha-synuclein (αSyn) within cells in the brain and gut, and the presence of inflammatory molecules called cytokines within the brain. In addition, 75 percent of people with PD have gastrointestinal (GI) abnormalities, primarily constipation.

To test if bacteria in the gut may contribute to PD, the researchers utilized mice that overproduce αSyn and display symptoms of Parkinson’s. One group of mice had a complex consortium of gut bacteria; the others, called germ-free mice, were bred in a completely sterile environment and thus lacked gut bacteria. The researchers had both groups of mice perform several tasks to measure their motor skills, such as running on treadmills, crossing a beam, and descending from a pole. The germ-free mice performed significantly better than the mice with a complete microbiome.

When gut bacteria break down dietary fiber, they produce molecules called short-chain fatty acids (SCFAs), such as acetate and butyrate. Previous research has shown that these molecules also can activate immune responses in the brain. Thus, the researchers hypothesized that an imbalance in the levels of SCFAs regulates brain inflammation and other symptoms of PD. Indeed, when germ-free mice were fed SCFAs, cells called microglia–which are immune cells residing in the brain–became activated. Such inflammatory processes can cause neurons to malfunction or even die. In fact, germ-free mice fed SCFAs now showed motor disabilities and αSyn aggregation in regions of the brain linked to PD.

In a final set of experiments, the researchers obtained fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients.

Paper: “Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease”
Reprinted from materials provided by CalTech.

For the first time, researchers have found higher levels of Gram-negative bacteria antigens in brain samples from late-onset Alzheimer’s disease patients. Compared to controls, patients with Alzheimer’s had much higher levels of lipopolysaccharide (LPS) and E coli K99 pili protein. In addition, the researchers also found LPS molecules congregated with amyloid plaques, which have been linked to Alzheimer’s pathology and progression. The research was published in Neurology.

Researchers have not yet determined if the bacteria are causing Alzheimer’s disease or a consequence of it.

Many Gram-negative bacteria are pathogenic, including E. coli, Helicobacter pylori, salmonella, Chlamydophila pneumoniae and Shigella. Researchers have known for some time that infections can increase the risk of Alzheimer’s; however, this is the first time anyone has found increased levels of Gram-negative bacteria antigens in Alzheimer’s disease brains and bacterial molecules associated with the disease pathology. This research follows previous animal studies that showed bacterial LPS plus ischemia/hypoxia can increase amyloid β and produce amyloid plaque-like aggregates.

The study compared 24 gray and white matter samples from patients with the disease – using Consortium to Establish a Registry for Alzheimer’s disease criteria – with 18 samples from people who had shown no evidence of cognitive decline. While LPS and K99 were found in both groups, the prevalence was much higher in the Alzheimer’s patients. K99 was found in nine of 13 Alzheimer’s gray-matter samples compared to one of 10 controls by Western blot analysis. Increased K99 levels were also found in Alzheimer’s disease white matter samples. The story was similar with LPS, which was found in all six samples (three gray and three white matter) but not in the controls by Western blot analysis.

The researchers spent four years validating these results before publishing. In particular, they were concerned about contaminated samples, as LPS is commonly found in many reagents. However, the differentials between the Alzheimer’s disease samples and controls and the unique localizations of the molecules in Alzheimer’s brains seem to indicate the team avoided this pitfall.

These findings highlight the need to further investigate how infectious agents impact Alzheimer’s. While discovering LPS and K99 in Alzheimer’s disease brain samples is a good start, researchers must study the role bacteria may play in the disease pathology. A proven link between bacterial infections and Alzheimer’s could offer new opportunities to prevent and treat the disease.

Paper: “Gram-negative bacterial molecules associate with Alzheimer disease pathology”
Reprinted from materials provided by the UC Davis MIND Institute.