Can Corynebacterium in the Gut Trigger Parkinson’s Disease?

SAN DIEGO—The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it may mean that Corynebacterium triggers Parkinson’s disease in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for Parkinson’s disease identified to date, but it is not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there is a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, Professor of Neurology and Genomics at the University of Alabama, Birmingham.

Haydeh Payami, PhD

Genotypes and Triggers

The finding, which was presented at the 142nd Annual Meeting of the American Neurological Association, may begin to clarify the link between the dozens of genetic risk factors for Parkinson’s disease and environmental triggers that lead to the disease. Different bacteria may be associated with different genetic risk factors. Eventually, the researchers aim to map out which genetic susceptibilities are associated with which elements of the microbiome and which genotypes are associated with other environmental factors, such as pesticides, Dr. Payami, leader of the multicenter neurogenetics research collaboration, said.

Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged patients with Parkinson’s disease and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their guts and then looked for interactions between rs356219 genotype, gut microbiome, and Parkinson’s disease risk.

The medical literature has been full of hints that Parkinson’s disease might be set off by something going wrong in the gastrointestinal (GI) tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in Parkinson’s disease are among the many clues. The goal of the work was to find the link between Parkinson’s disease and its GI aberrations.

Ninety genera were identified in the stool samples, but “no matter how you looked at the data, whichever method you used, one [genus] kept coming up” for interaction with the rs356219 genotype, “and that was Corynebacterium,” Dr. Payami said.

Heightened Risk

As in past studies, the rs356219 AA genotype did not increase the odds of Parkinson’s disease, and there was no difference in microbiome abundance between patients with Parkinson’s disease and controls. The GA genotype increased the odds slightly without Corynebacterium, but it increased the odds more than fivefold when Corynebacterium was in the gut (odds ratio, 5.9). If people had GG plus Corynebacterium, however, developing Parkinson’s disease was a certainty.

Corynebacterium was more abundant in GA subjects with Parkinson’s disease than in GA subjects without Parkinson’s disease, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had Parkinson’s disease.

Corynebacteria are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It is not clear how they get incorporated into the gut microbiome, or if they can be wiped out selectively in the gut with antibiotics or probiotics.

Perhaps Corynebacterium in the GI tract induces expression of alpha-synuclein protein, a major component of Parkinson’s disease Lewy bodies that is known to travel from the gut to the brain. Maybe the amount expressed depends on how many Gs people have in rs356219. Perhaps “if you have two Gs, you get so much alpha-synuclein that there is no turning back, and it is enough to cause Parkinson’s disease,” Dr. Payami said.

The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab. The study was supported by the NIH.

—M. Alexander Otto