REPORTING FROM ANA 2017
SAN DIEGO (FRONTLINE MEDICAL NEWS) – 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 means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.
It’s a potentially huge finding that begins to unravel the link between the dozens of genetic risk factors for PD and environmental triggers that push people over the edge. “ Corynebacterium isn’t the only bug. I think there are other bugs that go with other” genetic risk factors. Eventually, “we are going to map this whole thing out: Which bugs go with which genetic susceptibilities, and which genetic susceptibilities are triggered by” other things in the environment, such as pesticides, Dr. Payami, leader of the multicenter neurogenetics research collaboration, said in an interview.
Her team genotyped SNCA rs356219 from blood samples in 197 middle-aged PD patients and 115 age-matched controls. They also extracted DNA from stool samples to see what bacteria were in their gut and then looked for interactions between rs356219 genotype, gut microbiome, and PD risk.
The medical literature has been full of hints for a while now that PD might be set off by something going wrong in the gastrointestinal tract. Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in PD are among the many clues. The goal of the work was to find the link between PD 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.
As in past studies, the rs356219 AA genotype did not increase the odds of PD, and there was no difference in microbiome abundance between PD patients 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; P = .04). If people had GG plus Corynebacterium, however, “you nailed it,” Dr. Payami said: The odds of developing PD were infinite (P = .0003).
Corynebacterium was more abundant in GA subjects with PD than GA subjects without PD, but it was by far the most abundant in GG subjects, and every person who had the GG genotype and gut Corynebacterium also had PD.
Corynebacterium are gram-positive, aerobic bacilli commonly found on the skin. Some members of the genus are opportunistic pathogens. It’s 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 PD Lewy bodies that’s 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’s there’s no turning back, and it’s enough to cause PD,” Dr. Payami said.
The study was led by Zachary Wallen, a PhD candidate in Dr. Payami’s lab, and presented by him at the annual meeting of the American Neurological Association. The work was supported by the National Institutes of Health. Dr. Payami and Mr. Wallen had no industry disclosures.
SOURCE: Wallen Z et al. ANA 2017 abstract number S268