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AAN 2024 | The microbiome in Parkinson’s disease onset and exacerbation

Valentina Leta, MD, King’s College Hospital & King’s College London, London, UK, provides a background of gut health in Parkinson’s disease (PD) and outlines what is known about the role of the gut microbiome in disease onset and exacerbation. Some degree of gastrointestinal (GI) dysfunction is seen in all patients with PD, and clinical manifestations of GI dysfunction (including dysphagia, delayed gastric emptying, and constipation) can precede the onset of motor symptoms. Several mechanisms have been identified that may explain these disturbances, including alteration of the gut microbiome. This provides the rationale for the use of microbiome-modulating interventions, such as probiotics and fecal microbiota transplantation, in the treatment of PD. This interview took place at the American Academy of Neurology (AAN) Annual Meeting 2024 in Denver, CO.

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Transcript

Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction. The entire gastrointestinal tract can be affected from the mouth to the rectum. We know now that there are several mechanisms that can explain these gastrointestinal symptoms and disturbances, among them being the alteration of the gut microbiota. This is the pool of bacteria, protozoa and viruses which live in our gastrointestinal tract...

Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction. The entire gastrointestinal tract can be affected from the mouth to the rectum. We know now that there are several mechanisms that can explain these gastrointestinal symptoms and disturbances, among them being the alteration of the gut microbiota. This is the pool of bacteria, protozoa and viruses which live in our gastrointestinal tract. We know now that people with Parkinson’s have an altered gut microbiota compared to people without this condition, and the alterations seem to suggest pro-inflammatory changes. This is a situation that can trigger inflammation, and potentially also facilitate alpha-synuclein aggregation, which is involved in the pathogenesis of Parkinson’s disease and can be also found in the enteric nervous system at the level of the gastrointestinal tract.

Over the last decade, several studies have showed these changes in the gut microbiota of people with Parkinson’s. This has set the groundwork for the use of gut microbiota-modulating interventions such as probiotics or fecal microbiota transplantation for the treatment of Parkinson’s disease. Among the different clinical manifestations of gastrointestinal dysfunction in Parkinson’s disease, we have dysphagia, delayed gastric emptying and constipation. For instance, we know that constipation is one of the prodromal features of the disease, and is also a risk factor for the development of the condition. This highlights the importance of the gastrointestinal tract in Parkinson’s disease. These symptoms are prevalent, are common. They are troublesome for the patients, and they can also precede the onset of motor symptoms. From a pathological point of view, we know that the alpha-synuclein pathologic aggregations can be found in the enteric nervous system, which is essentially the so-called second brain because there are several neurons at this level. In people with Parkinson’s, post-mortem studies have shown the presence of pathological aggregations of alpha-synuclein in the enteric nervous system.

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