Lipids in microbiome-host interactions

We started to look at how gut microbes interact with fats in the diet with a study of dietary soy bean oil and its effect on Lactobacilli in the small intestine (Di Rienzi, 2018). This led us to think more broadly about the fats produced by gut bacteria themselves, and we chose to focus on a particular class of lipids, sphingolipids, because only a restricted group of Bacteria (i.e., the Bacteroidetes) make these lipids in the gut (Heaver, 2018). Through genetic manipulation of a prominent Bacteroides species (B. thetaiotaomicron) and studies in mice, we showed that the capacity to produce sphingolipid in the gut affect levels of sphingolipid (ceramides) in the liver (Johnson, 2020), which can be relevant for metabolic disease. We are now delving into other organ systems to assess how production of sphingolipids by gut bacteria affects the host sphingolipodome.

  • Di Rienzi SC, Jacobson J, Kennedy EA, Bell ME, Shi Q, Waters JL, Lawrence P, Brenna JT, Britton RA, Walter J and Ley RE. Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil fatty acids. eLife 7:e32581. (2018).
  • Heaver SL, Johnson EL and Ley RE. Sphingolipids in host-microbial interactions. Current Opinion in Microbiology 43: 92-99 (2018)
  • Johnson EL, Heaver SL, Waters JL, Kim BI, Bretin A, Goodman AL, Gewirtz AT, Worgall TS and Ley RE. Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Nature Communications 11:2471 (2020)
  • Di Rienzi S, Johnson E, Waters JL, Kennedy EA, Jacobson J, Lawrence P, Wang DH, Worgall TS, Brenna JT, and RE Ley. The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil. bioRxiv 2020.09.03.281626 (2020)
  • Heaver SL , H. H. Le, P. Tang, A. Baslé, J. Marles-Wright, E. L. Johnson, D. J. Campopiano, R. E. Ley. Inositol lipid synthesis is widespread in host-associated Bacteroidetes. BioRxiv  https://doi.org/10.1101/2021.04.26.441525 (2021)