Journal article
Host immunomodulatory lipids created by symbionts from dietary amino acids
SF Oh, T Praveena, H Song, JS Yoo, DJ Jung, D Erturk-Hasdemir, YS Hwang, CWC Lee, J Le Nours, H Kim, J Lee, RS Blumberg, J Rossjohn, SB Park, DL Kasper
Nature | NATURE PORTFOLIO | Published : 2021
Abstract
Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation1. However, little is known about the molecular mechanisms that control immune development in the host–microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from the human symbiont Bacteroides fragilis (BfaGCs). The characteristic terminal branching of BfaGCs is the result of incorporation of branched-chain amino acids taken up in the host gut by B. fragilis. A B. fragilis knockout strain that cannot metabolize branched-chain amino acids showed reduced bra..
View full abstractGrants
Awarded by National Institutes of Health
Funding Acknowledgements
We thank J. McCoy and E. J. Paik for manuscript preparation, R. T. Bronson for histopathological scoring, S. Iyer, L. Gebremedhin, E. Choi and T. Yanostang for technical assistance, and the staff at the Australian Synchrotron for assistance with data collection. This work was supported by National Institutes of Health (K01-DK102771 and R01-AT010268 to S.F.O., and R01-DK044319 to R.S.B.), Department of Defense (W81XWH-19-1-0625 to D.L.K.), Brigham and Women's Hospital (Department of Anesthesiology, Perioperative and Pain Medicine Basic Science Grant to S.F.O.), the National Research Foundation of Korea (2014R1A3A2030423 and 2012M3A9C4048780 to S.B.P.), and the Australian Research Council (ARC) (CE140100011 and ARC Laureate Fellowship to J.R., and ARC Future Fellowship to J.L.N.). Graphical images used for the Fig. 2 were created with BioRender.com.