Nature: Bile metabolites of gut microorganisms can enhance immune cells.

May 6, 2020 / / -- A study by the Ludwig Cancer Research Center (LCR) has found a new way in which colons in the small intestine can support the production of regulatory Treg, an immune cell that suppresses autoimmune response and inflammation.
Ludwig Alexander Rudensky, MSK's director, led the study, which was published in the journal Nature.
that a microbial metabolite, the organic acid isoDCA, promotes local production of immunosuppressive immune cells in the colon.
this locally occurring or "outer" Treg helps suppress chronic intestinal inflammation, which is the main cause of colorectal cancer.
While the study does not directly address cancer prevention, its findings have interesting revelations in this area -- which is why the study is partly funded by the Colon Cancer Prevention and Early Detection Initiative, launched in 2015 by the Ludwig and The Conrad N. Hilton Foundation.
photo source: Nature "People have been thinking about using symbiotic microbes to treat inflammatory colon diseases," Rudensky said.
"s approach is to develop a new drug made up of specific microorganisms that can limit inflammation, promote colon health and reduce people's risk of colon cancer.
groups of bacteria that produce ISoDCA and other metabolites can promote anti-inflammatory activity in colon immune cells, which may be part of these interventions.
" gut microbes are essential for digestion and metabolism, and they support many other important processes, from immunomodulation to brain development.
as an authority on Treg, Rudensky has long explored the intersection of symblotic bacteria and Treg.
is mainly mature in the thymus, but can also be induced by prebiotic cells in other tissues, especially the intestines.
he has shown that these peripheral Tregs protect beneficial gut microbes from immune attacks and suppress chronic intestinal inflammation.
two-way communication between the host and the symbic microbiome, and the host must understand the composition of the community and react to this information," Rudensky said.
means that one possible means of communication between the microbiome and the host immune system is through the metabolites of symbic bacteria, because metabolic support is one of the main services that symbic bacteria provide to the host.
" is pumped into the gut to help digest fat in the bile is retained in the intestine, some of which is metabolized by symbic bacteria.
Rudensky and his colleagues wondered whether metabolic by-products affect the local immune environment.
to find out, they screened the spectrum of bile acid produced by bacterial metabolism to observe this effect in the co-culture of T cells that produce Treg's pregenitor and the deducination cells that help guide Treg's production.
data show that two products of bacterial bile metabolism -- omega-MCA and isoDCA -- significantly improve the conversion of T-cell pregenes to extrinsic Treg.
Rudensky and his colleagues looked at isoDCA, which is high in the human intestine, and found that bile acid does not work on pregenuic T cells, but on dedes.
they found that IsoDCA could fight the signals sent by bile acid sensors in dextaline cells, known as the Farnister X-sensor (FXR).
this inhibits the expression of genes that cause protective immune responses, allowing them to enter an anti-inflammatory state, which drives the production of extrinsic Treg.
, Rudensky and his colleagues conducted synthetic biology experiments on mouse models to confirm the biological authenticity of their findings.
results were consistent with cell culture results.
mice that were modified to colonize bacteria that produced ISODCA had much fewer extrinsic Tregs in their intestines than those colonized by the same bacteria.
the same results apply to two other similar gut bacteria.
() References: Ludwig MSK study reveals bile metabolite of gut microbes boosts immune cells Campbell, C., McKenney, P.T., Konstantinovsky, D. et al. Edery metabolism of bile acids promotes generation of external regulatory T cells. Nature (2020). https://doi.org/10.1038/s41586-020-2193-0.