Gut commensals make choline too.
Nat Microbiol. Jan 2019. doi: 10.1038/s41564-018-0325-1
COMMENT: This article, within the section News and Views, comments the work of Chittim, L. C., Martinez del Campo, A. & Balskus E. P. in Nat Microbiol. 2019 Jan;4(1):155-163, about gut bacterial phospholipase D and its involvement in the generation of disease-associated trimethylamine.
Phospholipase D (PLD) enzymes from diverse members of the gut microbiota, as commensal ones as well as pathogenic ones, catalize the hydrolysis of phosphatidylcholine (PC) to choline, as we display in the Figure (at the right). This choline can be transformed in the disease-associated trimethylamine (TMA).
Gut commensal organisms play an important role in the conversion of choline to disease-associated TMA. By narrowing in on the biochemical activity of individual gut microorganisms, it was revealed that commensals can convert PC to choline using PLD enzymes. This process occurs in microorganisms that can (that is, those harbouring the CutC gene) and cannot further convert choline to TMA, which is then converted to TMAO by the host via FMO3 (flavin-containing monooxygenase 3).
Chittim et al. reveal the importance of microbial interactions in TMA production. They unexpectedly found PLDs in organisms that cannot metabolize choline to TMA, suggesting that these microorganisms are providing choline to choline-utilizers within the community
After analizing the similarity between PLDs the authors found that gut commensal PLDs enzymes differ from pathogenic PLDs and host PLDs and they realized that it would allow targeting commensal PLDs without impacting host PLDs. The authors highlight that the inhibition of commensal PLDs supposes a real therapeutic opportunity for treating TMA-induced pathologies via the inhibition of commensal PLDs.
TMAO has been implicated in a number of adverse host pathologies, such as cardiovascular disease. In the current study, the authors report that several microorganisms have phospholipase D (PLD) enzymes that produce choline from PC
Gut microbiome Phospholipase D enzymes are a new target for therapeutic intervention of host diseases associated with TMA production.