Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis, 2019, Song et al

[Andy]

In mice.

The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules1. Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins2. Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors3,4. These receptors have pivotal roles in shaping host innate immune responses1,5. However, the effect of this host–microorganism biliary network on the adaptive immune system remains poorly characterized.

Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3+ regulatory T (Treg) cells expressing the transcription factor RORγ. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this Treg cell population. Restoration of the intestinal BA pool increases colonic RORγ+ Treg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites.

Paywall, https://www.nature.com/articles/s41586-019-1865-0
Sci hub, https://sci-hub.se/10.1038/s41586-019-1865-0

ETA: Added "In mice".

 

[mariovitali]

cc @Perrier

Paywall, https://www.nature.com/articles/s41586-019-1865-0
Sci hub, https://sci-hub.se/10.1038/s41586-019-1865-0

This is spot on to what we should be looking at. Looking only to Gut microbiota and not Bile acids is a huge mistake IMHO. Recall that Naviaux et. al found impaired bile acids metabolism , as well as Germain et. al (with Maureen Hanson)

The pathway with the highest impact factor is the taurine and hypotaurine metabolism with taurine (28) as the central compound of this pathway (Fig. S4A). A decrease in concentration of this metabolite might reflect a general effect on this pathway and the consequences associated with the general metabolism of the body. Of important note, taurine is also part of the primary bile acid biosynthesis pathway where three of the near-final products (16, 19 and 28) are found to be reduced in patients according to our measurements (Fig. S4B). The main function of bile acids is to physically support the digestion of dietary fats.

The glyoxylate and dicarboxylate metabolism is another pathway with high pathway impact, with two major metabolites (20 and 36) both reduced in patients compared to controls (Fig. S4C). Of note, the glyoxylate cycle also allows humans to use fats for the synthesis of carbohydrates, a function interrelated to bile acids. One of the two pathways with the highest number of hits is the glycerophospholipid metabolism with five metabolites affected (52, 18, 6 and 56 decreases while 61 increases, Fig. S4D). This is another example of a lipid metabolism pathway, in this case, mainly lipids involved in biological membrane composition. The fatty acid biosynthesis and metabolism pathways also showed disturbances but all three of the acids affected (72, 73 and 74) had higher concentrations in patients vs. controls (Fig. S4E).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365380/

 

[lansbergen]

Bile is involved.

A greenish glow over the fresh stool was one of two symptoms that together with a dry cough told me the animals had a flare and needed levamisole.

The stools also looked as if the fat was not properly digested.