Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis

Brown, Eric; Ke, Xiaobo; Hitchcock, Daniel S.; Jeanfavre, Sarah; Ávila-Pacheco, Julián; Nakata, Toru; Arthur, Timothy D.; Fornelos, Nadine; Heim, Cortney E.; Franzosa, Eric A.; Watson, Nicki; Huttenhower, Curtis; Haiser, Henry J.; Dillow, Glen W.; Graham, Daniel B.; Finlay, B. Brett; Kostic, Aleksandar D.; Porter, Jeffrey A.; Vlamakis, Hera; Clish, Clary B.; Xavier, Ramnik J.

doi:10.1016/j.chom.2019.04.002

Cited by 329 publications

(355 citation statements)

References 53 publications

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“…For the gut microbiota lipid metabolites, a family of Bacteroides ‐derived sphingolipids were observed to maintain intestinal homeostasis and symbiosis. The depletion of fecal Bacteroides sphingolipids may serve as a marker for inflammatory bowel disease . Other microbial lipid metabolites such as conjugated linoleic acids were demonstrated to exhibit anti‐inflammatory effects and favorable cardiometabolic effects in animal studies .…”

Section: Microbial Metabolites Are Messengers In the Gut–systemic Aximentioning

confidence: 99%

“…Using these technologies, a broad coverage of various classes of small molecules, including carbohydrates, lipids, amino acids, biogenic amines, and many other organic acids, in clinical samples can be quantified and annotated . Untargeted metabolomics approaches have been increasingly used to explore disease‐associated metabolites from case–control studies . The identified disease–metabolite correlations can then be confirmed by a validation cohort.…”

Section: Discovery Of Gut Microbiota‐specific Bioactive Metabolitesmentioning

confidence: 99%

“…Moreover, potentially beneficial compounds for disease prevention and control could also be discovered from metabolome research targeting microbial metabolites. Xavier et al discovered a set of Bacteroides sphingolipid metabolites that can serve as protectants for inflammatory bowel disease by inhibiting the production of host ceramides . Undoubtedly, the gut microbial world is a treasure trove for the investigation of novel disease mechanistic pathways and drug discovery …”

Section: Discovery Of Gut Microbiota‐specific Bioactive Metabolitesmentioning

confidence: 99%

“…42,43 Untargeted metabolomics approaches have been increasingly used to explore disease-associated metabolites from case-control studies. 14,17,44 The TMAO is now generally regarded as an independent risk factor for CVD as well as a therapeutic target for the development of interventional approaches. 46 By adopting a similar approach, Bäckhed et al discovered that imidazole propionate, which is generated from the gut microbial metabolism of histidine, is an etiological compound for the development of type II diabetes.…”

Section: Discovery Of Gut Microbiota-specific Bioactive Metabolitesmentioning

confidence: 99%

“…8 Accumulating evidence suggests that microbiota-derived small molecules could be key messengers conveyed from gut microbes to other parts of the human body. [9][10][11][12][13][14] These small bioactive molecules, such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), imidazole propionate, conjugated linoleic acid, and s-equol, are derived mainly from the gut microbiota metabolism of dietary components such as dietary fibers, amino acids, fatty acids, and phytochemicals. [15][16][17][18][19] Studies have suggested that gut microbiotaderived metabolites play key roles in health maintenance and disease progression.…”

Section: Introductionmentioning

confidence: 99%

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Measurement of gut microbial metabolites in cardiometabolic health and translational research

Hsu

Sheen

et al. 2020

Rapid Comm Mass Spectrometry

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The human gut microbiota is a functioning endocrine organ and stands at the intersection between dietary components and health or disease. There are very many microbial metabolites with numerous structures and functions arising from the gut microbial fermentation of foods and become signals for biological communication in the human body. These small molecules can be absorbed and delivered to distant organs through the circulatory system to build the gut–systemic axis. The gut microbial metabolomes are thus believed to play important roles in regulating cardiometabolic health and provide opportunities in mechanistic research and new drug discovery. Measurement of these novel microbial metabolites in clinical samples may serve as a tool for investigating disease biomarkers. In the past decade, the development of untargeted and targeted metabolomics approaches using NMR, LC/MS, and GC/MS has contributed to the exploration of gut microbial metabolomes in cardiometabolic health and disease. Some important targets are currently being translated into clinical applications. In this review article, we introduce an oral carnitine challenge test developed as an example to demonstrate the potential applications in personalized nutrition based on the function of gut microbiota. It is a method taking the gut microbiota as a bioreactor and provides fermentable materials as inputs and measures the outputs of targeted microbial byproducts in the blood or urine. This challenge test may be extended to measure metabolites from microbial fermentation related to other endocrinological or inflammatory diseases. We review current gut metabolome research approaches and propose a gut microbial functional measurement using a challenge test. We suggest that the maturation in measuring gut microbial metabolites may provide an important piece to complete the puzzle of precision medicine.

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Section: Microbial Metabolites Are Messengers In the Gut–systemic Aximentioning

confidence: 99%

Section: Discovery Of Gut Microbiota‐specific Bioactive Metabolitesmentioning

confidence: 99%

Section: Discovery Of Gut Microbiota‐specific Bioactive Metabolitesmentioning

confidence: 99%

Section: Discovery Of Gut Microbiota-specific Bioactive Metabolitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Measurement of gut microbial metabolites in cardiometabolic health and translational research

Hsu

Sheen

et al. 2020

Rapid Comm Mass Spectrometry

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Glycolipids in Parkinson's disease: beyond neuronal function

Spanos

Deleidi

2023

FEBS Open Bio

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Glycolipid balance is key to normal body function, and its alteration can lead to a variety of diseases involving multiple organs and tissues. Glycolipid disturbances are also involved in Parkinson's disease (PD) pathogenesis and aging. Increasing evidence suggests that glycolipids affect cellular functions beyond the brain, including the peripheral immune system, intestinal barrier, and immunity. Hence, the interplay between aging, genetic predisposition, and environmental exposures could initiate systemic and local glycolipid changes that lead to inflammatory reactions and neuronal dysfunction. In this review, we discuss recent advances in the link between glycolipid metabolism and immune function and how these metabolic changes can exacerbate immunological contributions to neurodegenerative diseases, with a focus on PD. Further understanding of the cellular and molecular mechanisms that control glycolipid pathways and their impact on both peripheral tissues and the brain will help unravel how glycolipids shape immune and nervous system communication and the development of novel drugs to prevent PD and promote healthy aging.

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Highly efficient CRISPR‐mediated base editing for the gut Bacteroides spp. with pnCasBS‐CBE

Liang

Tan

2023

Biotechnology Journal

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Bacteroidales are the most abundant order of bacteria in the healthy human gut and have the potential as a therapeutic agent. We constructed a pnCasBS-CBE system for base editing in the Bacteroides thetaiotaomicron to expand their genetic toolkit, which is able to efficiently convert a C:G to a T:A in the genome. As a functional proof-of-concept, we used the pnCasBS-CBE system to successfully introduce nonsynonymous mutation and stop codons to the genes involved in carbohydrate metabolism.The system also allowed for multiplexed gene editing with a single plasmid, enabling efficient editing of up to four genes in a single experiment. Furthermore, the pnCasBS-CBE editing system was validated and successfully applied in four other non-model gut Bacteroides species for genome editing. An unbiased genome-wide SNPs analysis indicated that the pnCasBS-CBE system showed high fidelity and applicability.Thus, this study provides a powerful clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome editing toolbox for functional genomic analysis in Bacteroidales.

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Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis

Abstract: Highlights d Colonization with a sphingolipid-deficient Bacteroides strain is pro-inflammatory d Metabolomics describe Bacteroides sphingolipids and their biosynthetic pathway d IBD patients have decreased Bacteroides sphingolipids but increased host sphingolipids

Cited by 329 publications

References 53 publications

Measurement of gut microbial metabolites in cardiometabolic health and translational research

Measurement of gut microbial metabolites in cardiometabolic health and translational research

Glycolipids in Parkinson's disease: beyond neuronal function

Highly efficient CRISPR‐mediated base editing for the gut Bacteroides spp. with pnCasBS‐CBE

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