Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels

Johnson, Elizabeth L.; Heaver, Stacey L.; Waters, Jillian L.; Kim, Benjamin I.; Bretin, Alexis; Goodman, Andrew L.; Gewirtz, Andrew T.; Worgall, Tilla S.; Ley, Ruth E.

doi:10.1038/s41467-020-16274-w

Cited by 227 publications

(201 citation statements)

References 54 publications

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“…Sphingolipids have been shown to play an important role in promoting bacterial virulence and enhancing survival during stress ( 64 , 65 ). Interestingly, sphingolipids are more commonly studied in host-associated microbiomes and have been implicated in the development of metabolic disorders ( 66 , 67 ). One trait associated with multiple-resilient bacterial families, including Acetobacteraceae , Rhizobiaceae , Oxalobacteraceae , and Rhodospirillaceae , was broad antibiotic/antimicrobial resistance ( 68 – 71 ).…”

Section: Discussionmentioning

confidence: 99%

Biotic Interactions Are More Important than Propagule Pressure in Microbial Community Invasions

Albright

Sevanto

Gallegos‐Graves

et al. 2020

mBio

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Microbial probiotics are intended to improve functions in diverse ecosystems, yet probiotics often fail to establish in a preexisting microbiome. This is a species invasion problem. The relative importance of the two major factors controlling establishment in this context—propagule pressure (inoculation dose and frequency) and biotic interactions (composition of introduced and resident communities)—is unknown. We tested the effect of these factors in driving microbial composition and functioning following 12 microbial community invasions (e.g., introductions of many microbial invaders) in microcosms. Ecosystem functioning over a 30-day postinvasion period was assessed by measuring activity (respiration) and environment modification (dissolved organic carbon abundance). To test the dependence on environmental context, experiments were performed in two resource environments. In both environments, biotic interactions were more important than propagule pressure in driving microbial composition and community function, but the magnitude of effect varied by environment. Successful invaders comprised approximately 8% of the total number of operational taxonomic units (OTUs). Bacteria were better invaders than fungi, with average relative abundances of 7.4% ± 6.8% and 1.5% ± 1.4% of OTUs, respectively. Common bacterial invaders were associated with stress response traits. The most resilient bacterial and fungal families, in other words, those least impacted by invasions, were linked to antimicrobial resistance or production traits. Illuminating the principles that determine community composition and functioning following microbial invasions is key to efficient community engineering. IMPORTANCE With increasing frequency, humans are introducing new microbes into preexisting microbiomes to alter functioning. Example applications include modification of microflora in human guts for better health and those of soil for food security and/or climate management. Probiotic applications are often approached as trial-and-error endeavors and have mixed outcomes. We propose that increased success in microbiome engineering may be achieved with a better understanding of microbial invasions. We conducted a microbial community invasion experiment to test the relative importance of propagule pressure and biotic interactions in driving microbial community composition and ecosystem functioning in microcosms. We found that biotic interactions were more important than propagule pressure in determining the impact of microbial invasions. Furthermore, the principles for community engineering vary among organismal groups (bacteria versus fungi).

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Section: Discussionmentioning

confidence: 99%

Biotic Interactions Are More Important than Propagule Pressure in Microbial Community Invasions

Albright

Sevanto

Gallegos‐Graves

et al. 2020

mBio

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“…The altered levels of certain SM and PC species in hyperglycemic individuals under increased risk for CKD could be caused by fluctuations in their fatty acid profile, which influences the first rate-limiting step in de novo SM synthesis, due to nutritional oversupply, dyslipidemia (44) or gut microbiome (45). The severity of CKD correlates with increased levels of saturated and mono-unsaturated fatty acids (46) 11; 51; 52).…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Approaches Reveal Metabolic Signatures of Incident Chronic Kidney Disease in Individuals With Prediabetes and Type 2 Diabetes

et al. 2020

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Early and precise identification of individuals with pre-diabetes and type 2 diabetes (T2D) at risk of progressing to chronic kidney disease (CKD) is essential to prevent complications of diabetes. Here, we identify and evaluate prospective metabolite biomarkers and the best set of predictors of CKD in the longitudinal, population-based Cooperative Health Research in the Region of Augsburg (KORA) cohort by targeted metabolomics and machine learning approaches. Out of 125 targeted metabolites, sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0 were identified as candidate metabolite biomarkers of incident CKD specifically in hyperglycemic individuals followed during 6.5 years. Sets of predictors for incident CKD developed from 125 metabolites and 14 clinical variables showed highly stable performances in all three machine learning approaches and outperformed the currently established clinical algorithm for CKD. The two metabolites in combination with five clinical variables were identified as the best set of predictors and their predictive performance yielded a mean area value under the receiver operating characteristic curve of 0.857. The inclusion of metabolite variables in the clinical prediction of future CKD may thus improve the risk prediction in persons with pre-and T2D. The metabolite link with hyperglycemia-related early kidney dysfunction warrants further investigation.

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“…Surprisingly, hepatic sphingolipid levels were linearly related to microbial load in the cecum. In accord, the sphingolipid production capacity of the gut microbiome has recently been linked to sphingolipid levels in the liver [17]. Whether the gut microbiota act as a source of sphingolipids to the host or signal to alter host sphingolipid production and processing of sphingolipids remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil

Rienzi

Johnson

Waters

et al. 2020

Preprint

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Studies in mice using germfree animals as controls for microbial colonization have shown that the gut microbiome mediates diet-induced obesity. Such studies use diets rich in saturated fat, however, Western diets in the USA are enriched in soybean oil, composed of unsaturated fatty acids (FAs), either linoleic or oleic acid. Here we addressed whether the microbiome is a variable in fat metabolism in mice on a soybean oil diet. We used conventionally-raised, low-germ, and germfree mice fed for 10 weeks diets either high (HF) or low (LF) in high-linoleic-acid soybean oil as the sole source of fat. All mice, including germfree, gained relative fat weight and consumed more calories on the HF versus LF soybean oil diet. Plasma fatty acid levels were generally dependent on diet, with microbial colonization status affecting iso-C18:0, C20:3n-6, C14:0, and C15:0 levels. Colonization status, but not diet, impacted levels of liver sphingolipids including ceramides, sphingomyelins, and sphinganine. Our results confirm that absorbed fatty acids are mainly a reflection of the diet, and show that microbial colonization influences liver sphingolipid pools.

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Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels

Cited by 227 publications

References 54 publications

Biotic Interactions Are More Important than Propagule Pressure in Microbial Community Invasions

Biotic Interactions Are More Important than Propagule Pressure in Microbial Community Invasions

Machine Learning Approaches Reveal Metabolic Signatures of Incident Chronic Kidney Disease in Individuals With Prediabetes and Type 2 Diabetes

The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil

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