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Pub- lished online July 21, 2017. http://dx.doi.org/10. 1093/molbev/msx206. Choline Theft—An Inside Job Marina Mora-Ortiz 1 and Sandrine Paule Claus 1, * 1 Department of Food and Nutritional Sciences, University of Reading, Whiteknights Campus, PO Box 226, Reading RG6 6AP, UK *Correspondence: s.p.claus@reading.ac.uk http://dx.doi.org/10.1016/j.chom.2017.08.017 Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations. Choline is an essential nutrient abundant in diet, especially in high-protein-contain- ing food such as eggs, red meat, soy beans, and wheat germs. It is critical for neurotransmission (as it is the precursor of the neurotransmitter acetylcholine), for epigenetic regulation via the synthesis of the major methyl donor S-adenosylme- thionine (SAM), and is necessary to pro- duce phosphatidylcholine, the ubiquitous phospholipid that ensures the integrity of cell membranes (Zeisel, 2000). Choline’s essential nature has been widely evi- denced by studies in which choline defi- ciency results in abnormalities in epige- netic regulation and lipid metabolism (Lombardi et al., 1968; Pogribny and Beland, 2009). Following ingestion, some dietary choline is transformed by the gut microbial enzyme, choline trimethylamine (TMA) lyase, into TMA and acetaldehyde. TMA is then absorbed through the portal blood system and reaches the liver, where it is oxidized into trimethylamine- N-oxide (TMAO) by the host flavin mono- oxygenase 3 (FMO3) (Baker and Chaykin, 1962; Lang et al., 1998)(Figure 1). In an elegant investigation published in this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline metabolism by gut bacteria plays a signif- icant role in modulating host access to this resource (Romano et al., 2017). They first identified a choline-utilization gene cluster, cut, in a strain of E. coli (MS 200-1) isolated from the ileum of a healthy human donor. They show that this ‘‘type II’’ cut gene cluster encodes all the proteins required for anaerobic choline metabolism, including CutC and CutD, the choline-TMA lyase and its activase, respectively. Inspection of the genetic context of the cut gene cluster in g-Pro- teobacteria (of which E. coli is a member) allowed them to identify other genes potentially linked to choline usage absent in the type I cut cluster, which is abundant in Firmicutes, Actinobacteria, and d-Pro- teobacteria. Romano et al. (2017) then confirmed the role of the E. coli cut gene cluster in choline metabolism by knocking out cutC and cutD. These mutants were unable to grow on a restricted medium containing choline as the sole carbon source and failed to convert choline into TMA, demonstrating their essential involvement in TMA production from dietary choline. Next, they determined that the respiratory electron acceptors fumarate, nitrate, DMSO, and TMAO sup- ported bacterial growth on choline as a carbon source in anaerobic conditions. Given that nitrate is known to be released into the lumen during gut inflammation and that some E. coli sp. use it as an electron acceptor during anaerobic growth, Romano et al. (2017) hypothe- sized that the bacterial strains able to couple nitrate respiration with choline usage could bear an evolutionary advan- tage in the inflamed gut as previously sug- gested (Winter et al., 2013). Romano et al. (2017) further hypothe- sized that choline-consuming bacteria may have a significant impact on host choline-utilization pathways. To test this hypothesis, they developed a gnotobiotic model consisting of adult germ-free mice associated with a simplified gut micro- biota composed of five bacteria common in the human gut that are unable to metab- olize choline and added either a wild-type choline-consuming E. coli (CC + ) or a cutC knockout (DcutC) non-choline consuming mutant strain (CC ). Deletion of the cutC gene significantly impaired E. coli colonization, suggesting that choline- consuming E. coli receive a fitness advan- tage in vivo and that choline metabolism modulates the composition of gut bacte- rial communities. Importantly, CC + coloni- zation resulted in an altered host plasma metabolome, in which circulating levels Cell Host & Microbe Previews Cell Host & Microbe 22, September 13, 2017 ª 2017 Published by Elsevier Inc. 253