Demepivo
Dolores Abernathy
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Melbourne Bioinfromatics have published a loose transcription of Chris Armstrong's talk on his metabolomic research at the recent Stanford Symposium with the relevant slides.
https://www.melbournebioanalytics.org/metabolism-chris-armstrong-written-transcription/
https://www.melbournebioanalytics.org/metabolism-chris-armstrong-written-transcription/
What do we think is occurring in these patients? Given this information that we got from this metabolite data, we wanted to come with a broad mechanism that could describe what is occurring. We also had the microbe data, and we found significant differences in the bacteria between the two groups. We found an increase in certain bacteria that are a bit more scavenging in nature, the clostridium. And we have, in the past, also seen a lot of bacterial overgrowths.
We think that there is a long term low energy adaptation that happens over time. Because resources are being diverted away from other processes, and towards energy production, there are less cell proteins and cell fats being created which, in turn, means less enzymes and bile acids being created, which means two things: (1) that the body is less able to manage digestion within the small intestine, and (2) fewer fats and proteins feeding back into the blood (which negatively impacts energy metabolism).
With the intestines less able to digest fats and proteins, this means that they aren’t getting digested when they should be, and that they stay in the intestines a lot longer, and provide substrates for more bacteria to grow there. This results in changes in the gut microbiome, either with new bacteria, changes in bacteria or more growth of bacteria.
These bacteria have the ability to digest fats and protein, which they use to feed off. This may why we see an overgrowth and a change in these bacteria in ME/CFS. They can also digest these fats into smaller amino acids, fatty acids and into more short-chain fatty acids (via anaerobic metabolism in the colon).
Short-chain fatty acids are good for intestinal health, but once there are too many of them, they will overflow into the blood. Whilst they can be used by mitochondria for energy, they also can switch on AMPK as well. So it creates a kind of positive feedback loop, where AMPK can take protein away from enzymes. This is good for the bacteria, because they get more substrate (protein and fats), and so they create the sort of environment that keeps that going.
We want to know whether cellular proteins are being used in this way, and this is something we definitely would like to study in the future.