Sphingolipids in host–microbial interactions

Heaver, Stacey L.; Johnson, Elizabeth L.; Ley, Ruth E.

doi:10.1016/j.mib.2017.12.011

Cited by 181 publications

(157 citation statements)

References 52 publications

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“…IPA identified our input genes Vldlr and Sgms1 to be related to multiple lipid metabolism pathways (p-value = 5.23 x 10 -8 to 5.14 x 10 -4 ) (Figure S4, Table S8A) and DAVID functional annotation tool [Huang et al 2008] identified our genes Vldlr, Sgms1, and Asah2 to be related to lipid metabolism (p-value = 0.0048) as well as genes Sgms1 and Asah2 to be related to sphingolipid metabolism (p-value = 0.0063) ( Table S8B). Associations between gut microbiota and host lipid metabolism have been investigated previously, and proof of causality between specific microbial associations with lipid metabolism and sphingolipid production has been demonstrated [Ghazalpour et al 2016, Heaver et al 2018, Johnson et al 2019, Brown et al 2019].…”

Section: S4)mentioning

confidence: 99%

High-resolution QTL mapping with Diversity Outbred mice identifies genetic variants that impact gut microbiome composition

Schlamp

Zhang

Cosgrove

et al. 2019

Preprint

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The composition of the gut microbiome is impacted by a complex array of factors, from nutrient composition and availability, to physical factors like temperature, pH and flow rate, as well as interactions among the members of the microbial community. Many of these factors are affected by the host, raising the question of how host genetic variation impacts microbiome composition. Human studies confirm a role for host genetics, but opinions vary on just how important is host genetic variation in determining gut microbiome composition. The mouse model, by allowing far better control of genetics, nutrition, and other environmental factors, has provided an excellent opportunity to extend this work, and the Diversity Outbred (DO) mice in particular present a chance for mapping host genetic variants that influence specific attributes of microbiome composition. Here we apply 16s sequencing to fecal samples of 247 DO mice and perform QTL mapping on microbial abundances. In addition to finding a number of novel associations, the concordance with heritabilities and associations with both human and mouse studies was striking, including the phylum Tenericutes, family Ruminococcaceae, as well as Staphylococcus and Turicibacter.

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Section: S4)mentioning

confidence: 99%

High-resolution QTL mapping with Diversity Outbred mice identifies genetic variants that impact gut microbiome composition

Schlamp

Zhang

Cosgrove

et al. 2019

Preprint

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“…Although it exists as one of the major sphingoid bases in human milk (33), the interactions of dietary sphinganine (SA) and the gut microbiome remain largely unexplored. Prominent microbes of the infant gut have the capacity to synthesize sphingolipids (34) and the presence of microbiome-derived sphingolipids have been shown to be critical for proper immune system conditioning (35,36). Given that sphingolipids could enhance the fitness of these beneficial microbes, it is important to understand if and how dietary sphingolipids interact with the microbiome.…”

Section: Introductionmentioning

confidence: 99%

Dietary sphinganine is selectively assimilated by members of the gut microbiome

Lee

Johnson

2020

Preprint

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Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remain largely unknown. A class of lipids known as sphingolipids are bioactive components of most foods and are produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet-microbiome interactions.Here, we use a click-chemistry based approach to track the incorporation of bioorthogonal dietary omegaalkynyl sphinganine (sphinganine alkyne -SAA) into the gut microbial community (Click). Identification of microbe and SAA-specific metabolic products was achieved by fluorescence-based sorting of SAA containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together this approach, Click-Sort-Seq-Spec (ClickSSS), revealed that SAA-assimilation was nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAAtreated mice showed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activity via Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize 3 dietary sphingolipids. Therefore, ClickSSS provides a platform to study the flux of virtually any alkynelabeled metabolite in diet-microbiome interactions. 7 specific qualities of the alkyne, SAA-derived metabolites are revealed through the use of liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) (Spec).Application of Click-Sort-Seq-Spec (ClickSSS) (Fig. 1) revealed a set of microbes that take up dietary sphingolipids. This included the sphingolipid-producing Bacteroides and beneficial microbes such as Bifidobacterium that do not produce sphingolipids. Comparative metabolomics revealed the dietdependent sphingolipidome of both Bacteroides thetaiotaomicaron (B. theta) and Bifidobacterium longum subsp. infantis (B. longum). Our analysis suggests that diets rich in sphingolipids can influence the composition of the microbiome with implications for supporting the colonization of beneficial microbes. Moreover, ClickSSS can be applied to a variety of diet-microbiome systems to uncover the mechanism of nutrient interactions with the gut microbial metabolome.8 Materials and Methods General InformationAll buffer, reagents, media, and instrumentation were utilized sterile. All solvents used for metabolomics were purchased from Fisher Scientific as HPLC grade. Bacterial culturingBacteroides thetaiotaomicron strain V...

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“…In rainbow trout ( Oncorhynchus mykiss ), one of the most abundant commensal species residing in the skin and gills is Flectobacillus major (Lowrey, et al, 2015; Sepahi, et al, 2016), a bacterium that has the unique ability to synthesize glycosphingolipids (Batrakov, et al, 2000; Batrakov, et al, 1999). Recent studies in the mammalian gastrointestinal tract suggest that dietary sphingolipids or sphingolipids produced by bacteria can be absorbed by enterocytes in a number of ways including fusion of outer-membrane vesicles with host cell membranes (Heaver, et al, 2018). Absorbed sphingolipids are then mostly converted to free fatty acids and incorporated into triglycerides that enter the bloodstream in the form of chylomicrons (Heaver, et al, 2018) allowing for effects at distal sites.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies in the mammalian gastrointestinal tract suggest that dietary sphingolipids or sphingolipids produced by bacteria can be absorbed by enterocytes in a number of ways including fusion of outer-membrane vesicles with host cell membranes (Heaver, et al, 2018). Absorbed sphingolipids are then mostly converted to free fatty acids and incorporated into triglycerides that enter the bloodstream in the form of chylomicrons (Heaver, et al, 2018) allowing for effects at distal sites. Uptake mechanisms at other tissue barriers such as the gills or skin have not been investigated, but sphingolipid-derived metabolites such as ceramide and S1P can be taken up by cells by different mechanisms including binding to G-protein coupled receptors (Blaho and Hla, 2014).…”

Section: Introductionmentioning

confidence: 99%

Symbiont-derived sphingolipids regulate inflammatory responses in rainbow trout (Oncorhynchus mykiss)

et al. 2018

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Farmed fish live in association with diverse bacterial communities that produce wide arrays of metabolites. In rainbow trout, the skin and the gills are colonized by Flectobacillus major, a bacterium known to produce sphingolipids (SLs). The goal of this study is to evaluate the ability of F. major SLs to regulate rainbow trout inflammatory responses. F. major SLs were delivered by themselves or in combination with Freund’s Complete Adjuvant (FCA), an oil-based adjuvant known to cause severe abdominal inflammation when injected to fish. Trout injected with SL + FCA showed decreased severity of FCA toxic effects including necrosis, granuloma formation and presence of oil droplets. However, inclusion of SLs in the FCA preparation did not decrease infiltration of immune cells intramuscularly at the site of injection. Intraperitoneal or intravenous delivery of F. major SLs resulted in increased expression of IgT, IgM and TGFβ transcripts in the gills but not the head-kidney and had no effects on IL-10 expression. These results indicate the F. major SLs regulate rainbow trout inflammatory responses and indicate that this compound can have important applications in farmed fish health management.

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Sphingolipids in host–microbial interactions

Cited by 181 publications

References 52 publications

High-resolution QTL mapping with Diversity Outbred mice identifies genetic variants that impact gut microbiome composition

High-resolution QTL mapping with Diversity Outbred mice identifies genetic variants that impact gut microbiome composition

Dietary sphinganine is selectively assimilated by members of the gut microbiome

Symbiont-derived sphingolipids regulate inflammatory responses in rainbow trout (Oncorhynchus mykiss)

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