(P20-007-23) Dietary Choline in Host-Microbiome Interactions

Objectives: The gut microbiome can generate bioactive metabolites from dietary choline that affect host physiology. Much emphasis has been placed on the microbial metabolism of dietary choline and its association with cardiovascular disease through the production of trimethylamine, which enters the host’s circulatory system and is oxidized to trimethylamine N-oxide (TMAO) in the liver. However, there is potential for gut microbes to produce other choline-derived metabolites that may provide insight into the various ways that choline consumption affects microbiome function and host health.

Objectives: We hypothesize that we can detect previously uncharacterized choline-dependent gut microbiome interactions and resultant bioactive metabolites using a workflow created in our research group to trace nutrients through host-microbe systems.

Methods: Using techniques in bioorthogonal chemistry, sorting, sequencing, and mass spectrometry (BOSSS), we have created a workflow to isolate gut microbes that take up and modify dietary inputs. We have applied this workflow to investigate how gut microbes interact with dietary choline by introducing a traceable alkyne-modified choline [propargylcholine (PC)] molecule to mice. Microbiome samples and host tissue were collected at the time of sacrifice and analyzed for the presence of diet-derived alkyne-containing metabolites using click chemistry and comparative metabolomics.

Results: Preliminary data has confirmed that multiple gut microbes interact with dietary choline in the ileum of the mouse intestinal tract and that these microbes can be sorted into choline-interacting versus non-interacting populations. Profiling these sorted communities using high-throughput sequencing will determine important microbes involved in dietary choline metabolism. Dietary choline and its derivatives were also detected in the intestines, pancreas, liver, and brain of PC-consuming mice.

Conclusions: Choline-interacting microbes that interact with host metabolites derived from dietary choline can be identified using the BOSSS workflow. This ability to further define choline-dependent gut microbiome interactions will contribute to efforts to use diet to modulate the gut microbiome.

Funding Sources: NIH NIGMS, 2022 GEM PhD Employer Fellowship