Bile acid metabolites control TH17 and Treg cell differentiation, 2019, Hang et al

In mice.

Paywall, https://www.nature.com/articles/s41586-019-1785-z
Sci hub, https://sci-hub.se/10.1038/s41586-019-1785-z

 

cc @wigglethemouse @Perrier

From the paper @Andy linked above :

I wonder if this is all connected : Bile acids dysregulation -> NLRP3 activation , CD8 memory cells, DRP1 Mito fission / fusion , Lactate metabolism, Fatty acids oxidation, tryptophan metabolism. All of these concepts we have seen can be found in the following paper :









Title : Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism


https://www.frontiersin.org/articles/10.3389/fimmu.2018.01605/full

 

This sounds like it could be related to ME. I am only pooing fatty, gooey stuff for years.

 

This is major, please show to Dr. Davis someone!

 

Given the paper found by @Andy, i went through my emails and found the e-mail i sent to Derya Unutmaz regarding Bile Acids dysregulation. Derya replied that he is looking at the work of Dr. Mark Sundrud on Bile acids metabolism. With a bit of searching i found the following paper :


https://www.nature.com/articles/s41385-019-0162-4


From the paper we see the following figure :




Observe the bottom left corner where the immunomodulatory microbial metabolites are mentioned but more importantly Indole derivatives which rings a bell on what Ron Davis said about ME patients not having sufficent levels of "Indole propionate". The paper also discusses TH17 regulation.

 

Bile acids also affect C Difficile ( daughter has high toxin levels of both C Diff A and B but within (low) normal range on total bile acids)
https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(18)30335-0

https://www.nature.com/articles/s41522-019-0087-4
eta second ref

 

The problem is that apart from the level of bile acids, we have to look at the composition of them. Both Naviaux and Hanson found issues in the composition of Bile acids in ME patients. We will have to replicate these findings in a larger cohort.