So basically, this study looked at the effects of the gut microbiome and its composition on the brain volumes in people who are in their pre-clinical stage of Alzheimer’s disease. So basically, these are people who haven’t actually started showing symptoms. And these people are sampled through usually family history and enrichment of the APOE allele. So basically, we had 155 participants from the Wisconsin Registry of Alzheimer’s Prevention and the ADRC, the Alzheimer’s Disease Research Center here in Madison, Wisconsin...
So basically, this study looked at the effects of the gut microbiome and its composition on the brain volumes in people who are in their pre-clinical stage of Alzheimer’s disease. So basically, these are people who haven’t actually started showing symptoms. And these people are sampled through usually family history and enrichment of the APOE allele. So basically, we had 155 participants from the Wisconsin Registry of Alzheimer’s Prevention and the ADRC, the Alzheimer’s Disease Research Center here in Madison, Wisconsin. So we recruited these participants from those registries. And so basically most of them already had MRI studies already due to the condition. And so that was how we kind of, we do process the MRI studies and extract data from it, like the gray matter volumes, the white matter volumes, from that we can get the total brain volumes. And very importantly, we also look at the hippocampal volume. And throughout this interview, I might be mentioning the hippocampus a lot because this is one of the first key structures in the brain that get atrophied when a person starts to show symptoms of Alzheimer’s disease. Even before they start to show symptoms, you realize that there is evidence of atrophy of the hippocampus. And it’s also very essential for memory and learning. And so for that reason, we see that the people who move on to the clinical phase tend to have memory issues. They are unable to learn as they used to. And that’s why this metric is kind of very key to us. We also look at their CSF volume and things like we computed the atrophy index, which is basically the ratio of the CSF volume to the total brain volume. Because as the brain starts to atrophy, there’s going to be more space and space needs to be filled. And so the CSF fills that space. So that’s like from the cranial end of things. From the microbiome end of things, we asked these participants to give us stool samples. And these stool samples were processed using the 16S ribosomal RNA sequencing methods. And so we looked at specific taxa, different phylum, family, all of that, the genus, we looked at it broadly. And we analyzed that data using Bayesian model while also controlling for things like age, sex, total intracranial volume, biomarker status. And one of the important things we also controlled for is the interval between the MRI and the stool sample, because between those times, there’s the possibility of having some degenerative changes. And for those, we use the FDR control methods to make sure we’re controlling for that adequately. And so we have data from the microbiome studies and we have the brain volumes. So now what we wanted to do is to see whether there is any association between the two. Do we see more of maybe this taxa in people with lower hippocampal volumes and such? So basically, after running all of our analysis, we did first look at age and how it was related to gray matter, white matter and, you know, hippocampal volume and even atrophy. And as we expected, it tracked really well with existing data, which is that with age, we tend to lose brain volume and we tend to have more CSF because CSF has to fill up the spaces when there is atrophy. And we also looked at amyloid status and we saw that people who were amyloid positive, even before they started to show symptoms, they had smaller hippocampal volumes. So meaning they have begun to show symptoms of evidence of atrophy in the hippocampus. Same thing for phosphorylated tau. Those who were positive for that also had lower gray matter volumes. And we saw like several tags that track in the neurodegenerative markers. For example, generally we saw that the tags that produced short-chain fatty acids, they tend to show inverse associations with atrophy, meaning whenever you have more of those short-chain fatty acids producing taxa, we see less atrophy. So we kind of see some protective effects of those bacteria or microbiota. And so we saw things like that, like something like Romboutsia hominis was positively associated with hippocampal volume. So the more of those you have, the more intact your hippocampus seems to be and vice versa. So these were things that we saw. The interesting thing is that not all of these aligned across metric. We would see some tags that would show lower hippocampal volume, but then intact global brain volume. So that also clued us into thinking, yeah, there is some sort of region-specific effect. Like a person could have low hippocampal volume and have an intact general cortical volume. And so that tells us also that thinking about subcortical structures and not just globally what’s going on is very important in understanding the pathophysiology of Alzheimer’s disease.
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