No, Alzheimer’s disease is not caused by the gut microbiome.

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What is toilet obsession? It seems that scientists around the world are becoming increasingly interested in the contents of our gut and the seemingly enormous impact that all the different bacteria in it – our “microbiome” – can have on our risk of disease.

And it’s not just gut diseases: many researchers are exploring whether broader diseases might be linked to the health of our gut. New research in a specialized journal Brain claim to have discovered what they call “a causative role of gut microbiota in Alzheimer’s disease.”

Could your internal bacteria cause, or at least contribute to, dementia? If this were true, it would be important: it could potentially alter a person’s gut microbiome to reduce the risk of cognitive decline later in life. So is this true?

Big pile of monsters

The study revolves solely around stool samples. The researchers took one of 54 people with Alzheimer’s disease and 41 people without it.

They first wanted to find out whether the microbiome was different in people with more or less severe forms of Alzheimer’s disease. All participants took a cognitive test—a simple “screen” for problems with memory, thinking, or pattern recognition—and then the researchers correlated the test results with levels of different types of gut bacteria.

They claimed to have discovered a “microbiome signature of cognitive performance in Alzheimer’s disease.” Aber Sie stimmen vielleicht nicht zu: Von den dreizehn verschiedenen Bakterienarten, die sie untersucht haben, waren nur vier statistisch signifikant mit dem kognitiven Score verknüpft – und von diesen befanden sich drei nur an der Grenze der statistischen Signifikanz (ich kann Ihnen nicht sagen, was This). actual score). The size of the correlation is due to the fact that these numbers, as far as I know, are not reported anywhere – they are simply given as a “heat map” with different colors for different numbers – this is all fine for illustrative purposes, but why not? Do magazines insist that real numbers be included somewhere?).

Thus, there is no certainty that there was a reliable relationship between cognitive performance and gut bacteria counts, but again, with only 54 Alzheimer’s disease samples, it is perhaps unsurprising that few were found.

However, let’s assume there’s a strong connection here: your cognitive abilities are linked to your microbiome (other studies have claimed to have found something similar). What would that mean? This doesn’t necessarily mean the bacteria caused the cognitive differences: what if people with more severe Alzheimer’s eat differently than those without it, and this affects their gut bacteria?

This seems very plausible – and it would mean that the metaphorical arrow of the cause of Alzheimer’s disease is directed towards the microbiome, and not vice versa (or it could be that some other unknown third factor is driving the differences in microbiome and cognitive factors). . Let’s look at this below.

Enter the rats

That’s the most unpleasant thing. There’s no way to put it delicately, so I hope you didn’t just eat something. Researchers took several rats and gave them antibiotics to clear out their microbiome. They then replaced these microbiomes by seeding them with gut bacteria from people with or without Alzheimer’s disease.

This involved mixing samples of human feces into a “slurry” (in their words) and force-feeding it to rats. 15 rats received a suspension for Alzheimer’s disease; 15 received manure from healthy people.

One would hope that something like this would be worth experimenting with. It was? The first thing they did was observe the rats’ behavior in an IQ test that required them to perform certain tasks that required them to remember locations in cages or mazes that they had previously been shown.

Although the researchers claimed to have found some differences here, it all came down to how to measure them: there were statistically significant differences between the two groups on some memory measures; for many others this was not the case. Here again, as in the human correlation part of the study mentioned above, many of the differences were within the threshold, meaning that a slightly different sample could mean no effect was found.

So far so weak. But that is not all. They then examined the rats’ brains, paying particular attention to a part of the brain known to be associated with memory: the hippocampus. The hippocampus may develop new neurons (brain cells) that appear to help create new memories. In Alzheimer’s disease, this process of creating new neurons (“neurogenesis”) appears to be disrupted.

The researchers found that rats’ hippocampal neurogenesis differed depending on whether they were colonized with the microbiome of an Alzheimer’s disease patient. But at this point they were definitely comparing small samples: sometimes just four brain samples in each group (neurogenesis is hard to measure, I guess). Even then, not all the different measures of neurogenesis showed results. We will need a much larger replication study before we can put much weight on these extremely preliminary results.

There is a more serious problem. Yes, the hippocampus is affected in Alzheimer’s disease, and perhaps part of it is the ability to create new neurons. However, the main characteristic of Alzheimer’s disease is the death of brain cells: the technical term is “neurodegeneration.” The brain literally shrinks due to the loss of neurons (this also leads to the formation of plaques and protein tangles, which many, but not all, scientists believe also contribute to cognitive symptoms).

By basing the brain part of the study solely on this dimension of neurogenesis, I feel like we’re missing something. If you had asked me before reading this study what a “rat model” of Alzheimer’s disease would look like, I would have mentioned “impaired neurogenesis” as part of it, but I would have focused on neurodegeneration. This was not taken into account in the new study, which means that the Alzheimer’s disease model appears very incomplete.

Solution

There is more to the study than what I have described above. I wouldn’t discuss all these different tests. But it’s all the same story: very small sample sizes, very borderline results, and the feeling that even if all the results were completely reliable, we still wouldn’t be sure what exactly it would tell us about Alzheimer’s disease. Cognitive measures in rats may or may not be associated with cognitive impairment in humans with Alzheimer’s disease; The brain measurements examined only a lesser-known aspect of what we know happens to the brain of a person with dementia.

And remember the problem I mentioned at the beginning: are we sure that the microbiome of an Alzheimer’s patient is different? due to her Alzheimer’s disease? Unless we can be sure (and I don’t think we can because Alzheimer’s disease may affect their behavior and therefore their microbiome, perhaps as a result of changes in their diet), we certainly cannot conclude that differences in the microbiome lead to symptoms of dementia.

And yet, this is exactly what the article claims. Given the data, I would say that such assertive statements were more than premature. The study is not feasible, but also inconclusive.

Science Link of the Week

How cool is that? In the US, you’ll soon be able to get a needle-free flu vaccine without a prescription (you blow it through your nostril) and administer it at home. Since we need to make it as easy as possible to get vaccinated against the flu (and any other disease for which there is a vaccine!), this is good news. Let’s hope the UK follows suit.

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