Prevotella copri variants among a single host diverge in sphingolipid production

• Published in: mBio Vol. 15; no. 2; p. e0240923
• Main Authors: Xiao, Xieyue, Le, Henry H, Lee, Min-Ting, Lamm, Daniel, Johnson, Elizabeth L, Brito, Ilana L
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 14.02.2024
• Subjects: Host-Microbial Interactions; host–microbe interactions; microbiome; Prevotella; Prevotella copri; Research Article; sphingolipids; Prevotella copri; Prevotella; host–microbe interactions; sphingolipids; microbiome
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.02409-23

Sphingolipids serve as vital structural and signaling components of the cell membranes in both eukaryotes and prokaryotes. Within the gut microbiome, species have been identified as major producers of sphingolipids, and -produced sphingolipids have been shown to be modulators of host immune and metabolic functions. While species are a prominent feature of the gut microbiomes of populations living in industrialized countries, , a member of the same phyla, albeit a different family, is the dominant feature across the remainder of the global population, although their sphingolipid-producing capabilities have not been as thoroughly investigated. To fill this gap, we examined the genomes of over 60 diverse isolates of and identified several key enzymes involved in sphingolipid synthesis in . Combining bioorthogonal labeling and liquid chromatography-mass spectrometry (LC-MS) based lipidomics, we functionally characterized the first step in sphingolipid synthesis in addition to profiling the sphingolipidomes of strains, identifying key enzymes that may play roles in producing a diverse set of sphingolipids. Given the limited genetic engineering tools amenable for use in , our approach takes advantage of comparative genomics and phenotypic profiling to explore sphingolipid production in these understudied, yet highly prevalent, organisms.IMPORTANCESphingolipids are important signaling molecules for maintaining metabolic and immune homeostasis in the host. These lipids are also produced by gut commensals, most notably by species. Despite the global prevalence of in gut microbiomes of individuals, little is known about the types of sphingolipids they produce and whether they are similar in composition and structure to those produced by . Given the varied associations of with diverse sphingolipid-related health outcomes, such as rheumatoid arthritis and glucose intolerance, it is important to first characterize the specific sphingolipids produced by individual strains of and to identify the genes involved in their pathways of production. This characterization of -derived sphingolipids provides further insight into how bacterial sphingolipid production can serve as a mechanism for microbial modulation of host phenotypes.