Gut Microbiome Changes May Identify Parkinson's Disease Risk Years Before Symptoms

Changes to microbes that live in the gut can identify people at greater risk of Parkinson's disease long before symptoms develop, according to work that also raises hopes for new therapies. Researchers discovered signature changes in the gut microbiome that are more pronounced in people with a genetic risk for Parkinson's and even more stark in those diagnosed with the disease. The signature could help doctors spot patients at risk of Parkinson's years before they display clear symptoms and suggests that healthier diets and treatments that reshape the microbiome might prevent or delay the disease. Prof Anthony Schapira, the head of clinical and movement neurosciences at University College London and lead investigator on the study, said it was the first time a microbial signature in Parkinson's patients had been seen in people with a genetic susceptibility but had yet to develop symptoms. The signature appears to become stronger as the disease progresses. "These same changes can be found in a small proportion of the general population that may put them at increased risk," Schapira said. Cases of Parkinson's have doubled in the past 25 years, with more than 8.5 million people globally now living with the condition. The disease causes progressive brain damage, leading to tremors, slow movement and stiff and inflexible muscles. Patients often experience depression, anxiety, sleep and memory problems, and difficulty with balance. Parkinson's is driven by neurons dying in part of the brain called the substantia nigra. The loss of the nerve cells leads to a fall in dopamine in the brain, which is responsible for many of the disease's symptoms. There is no cure, but medicines that bolster dopamine can help, alongside physiotherapy and surgery. The UCL team analysed clinical and faecal data from 271 Parkinson's patients, 43 people with a risk gene for the disease but no clinical symptoms, and 150 healthy people. The abundance of more than a quarter of the gut microbes, or 176 species, differed in those with Parkinson's disease compared with the healthy group. The changes were not driven by medication. A similar pattern was seen in those genetically predisposed to Parkinson's but who did not have symptoms. The scientists corroborated the findings in further medical data from 638 people with Parkinson's and 319 healthy controls from the UK, South Korea and Turkey. A small proportion of healthy people had the microbiome signature, suggesting they were potentially at risk of the disease, according to Nature Medicine. It is unclear whether the microbial signature drives Parkinson's or vice versa, or both, but Schapira said changes in the microbiome could alter the production of a protein called alpha-synuclein, which plays an important role in damaging neurons in the disease. "Certain bacteria cause inflammation in the gut wall that increases alpha-synuclein, which is then transported up the vagus nerve from the gut to the brain and then into the brain cells affected in Parkinson's," he said. The vagus nerve carries information between the brain and major organs. Further work and clinical trials are needed to understand how gut microbes are linked to Parkinson's and whether reshaping the microbiome could shield against the disease, but dietary changes may help. In the study, people with the abnormal microbiome signature ate more processed foods and saturated fats rather than fruit, vegetables, fibre, fish and lentils. Claire Bale, an associated director of research at Parkinson's UK, said the study added to growing evidence that the gut microbiome was important in Parkinson's. "The findings indicate that changes in the microbiome may occur in the very early stages of the condition and that the extent of these changes may correlate with disease progression," she said. "Over the past decade, we have seen the impact of physical activity on managing symptoms and potentially slowing the course of the condition. Our growing understanding of the gut microbiome offers similar hope that dietary modification could benefit those living with Parkinson's."