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EAN 2021 | Can we achieve a clinically actionable test of the gut microbiome for neurodegenerative disorders?

Mounting evidence is implicating the gut microbiome in the pathogenesis of neurodegenerative disorders such as Parkinson’s disease (PD). Filip Scheperjans, MD, PhD, Helsinki University Central Hospital, Helsinki, Finland, talks on the challenge of designing a robust test of the microbiome that would be clinically useful for patients with neurodegenerative disorders and outlines the ongoing work aiming to achieve this goal. Current technologies are highly time consuming and can suffer from batch effects, limiting their clinical utility. Work is underway to establish a more rapid test that can determine if a PD patient has an abnormal microbiome composition. This would allow the identification of patients most likely to benefit from a treatment targeting gut changes. This interview took place during the European Academy of Neurology 2021 congress.

Transcript (edited for clarity)

In terms of a test, I think it’s not probably too far away, so we will need to come up, I think, with a method that is robust across different time points, meaning that in the traditional methodology that is being used. So sequencing-based analysis of microbiota, there’s actually quite some, what we call, batch effects that can be introduced. Meaning that data that has produced it, was produced at two different time points...

In terms of a test, I think it’s not probably too far away, so we will need to come up, I think, with a method that is robust across different time points, meaning that in the traditional methodology that is being used. So sequencing-based analysis of microbiota, there’s actually quite some, what we call, batch effects that can be introduced. Meaning that data that has produced it, was produced at two different time points. Even from the same dataset can look differently, which can be related to really just technical bias that is introduced during sample processing and so on. So, this is a problem and also the problem is that these analyses are quite time consuming, so they require quite a lot of bioinformatics. For a clinical context, it’s a bit difficult to use these.

But what we have been now trying to establish is a more rapid microbiome test, so we have been using a different method that is actually based on hybridization and fluorescence-based analysis of a certain restricted set of bacteria and so, we get to a turnaround time of a fecal sample analysis to about one to two weeks. So, we will be able to determine for a Parkinson’s patient, whether his or her microbiota composition is abnormal as we have seen it in Parkinson’s disease in other cohorts, or whether it is more similar to the general population. Because it actually seems that it’s not all Parkinson’s patients that have an abnormal microbiome, so it seems to be a significant subgroup of patients. So, this is probably the group that most likely would benefit from a treatment that is targeting the microbiome.

I think we’re making good progress in that respect and we’re currently actually using this new test method to screen patients for a fecal microbiome transplant trial that we’re currently conducting. So, I think this is a very important point to really understand that the microbiome, I think, will probably turn out to be one among several biomarkers that we can use to characterize a Parkinson’s patient. Because we’re dealing with a heterogeneous disorder, different factors have different roles in different patients and different, let’s say, impact in different patients.

By combining these biomarkers, we can better understand what is actually in this specific patient, the abnormalities and pathological changes that have led to Parkinson’s, so that we can address these in a, kind of, precision medicine approach. So, I think this is the way we’re going currently to really use the microbiome as a biomarker to phenotype the Parkinson’s patients, basically.

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Disclosures

Dr Scheperjans is founder and CEO of NeuroInnovation Oy and NeuroBiome Ltd., is a
member of the scientific advisory board and has received consulting fees and stock options from Axial Biotherapeutics.