Martin F Overbeek, Femke Rutters, Max Nieuwdorp, Mark Davids, Irene van Valkengoed, Henrike Galenkamp, Bert-Jan van den Born, Joline W J Beulens, Mirthe Muilwijk
{"title":"血浆鞘磷脂介导 HELIUS 队列中肠道微生物组组成与 2 型糖尿病风险之间的关系:一项病例队列研究。","authors":"Martin F Overbeek, Femke Rutters, Max Nieuwdorp, Mark Davids, Irene van Valkengoed, Henrike Galenkamp, Bert-Jan van den Born, Joline W J Beulens, Mirthe Muilwijk","doi":"10.1136/bmjdrc-2024-004180","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether sphingolipids mediate the association between gut microbiome and T2D, using data from the Healthy Life in an Urban Setting study.</p><p><strong>Research design and methods: </strong>Participants were of Dutch or South-Asian Surinamese ethnicity, aged 18-70 years, and without T2D at baseline. A case-cohort design (subcohort n=176, cases incident T2D n=36) was used. The exposure was measured by 16S rRNA sequencing (gut microbiome) and mediator by targeted metabolomics (sphingolipids). Dimensionality reduction was achieved by principle component analysis and Shannon diversity. Cox regression and procrustes analyses were used to assess the association between gut microbiome and T2D and sphingolipids and T2D, and between gut microbiome and sphingolipids, respectively. Mediation was tested familywise using mediation analysis with permutation testing and Bonferroni correction.</p><p><strong>Results: </strong>Our study confirmed associations between gut microbiome and T2D and sphingolipids and T2D. Additionally, we showed that the gut microbiome was associated with sphingolipids. The association between gut microbiome and T2D was partly mediated by a sphingolipid principal component, which represents a dominance of ceramide species over more complex sphingolipids (HR 1.17; 95% CI 1.08 to 1.28; proportional explained 48%), and by Shannon diversity (HR 0.97; 95% CI 0.95 to 0.99; proportional explained 24.8%).</p><p><strong>Conclusions: </strong>These data suggest that sphingolipids mediate the association between microbiome and T2D risk. Future research is needed to confirm observed findings and elucidate causality on a molecular level.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261679/pdf/","citationCount":"0","resultStr":"{\"title\":\"Plasma sphingolipids mediate the association between gut microbiome composition and type 2 diabetes risk in the HELIUS cohort: a case-cohort study.\",\"authors\":\"Martin F Overbeek, Femke Rutters, Max Nieuwdorp, Mark Davids, Irene van Valkengoed, Henrike Galenkamp, Bert-Jan van den Born, Joline W J Beulens, Mirthe Muilwijk\",\"doi\":\"10.1136/bmjdrc-2024-004180\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether sphingolipids mediate the association between gut microbiome and T2D, using data from the Healthy Life in an Urban Setting study.</p><p><strong>Research design and methods: </strong>Participants were of Dutch or South-Asian Surinamese ethnicity, aged 18-70 years, and without T2D at baseline. A case-cohort design (subcohort n=176, cases incident T2D n=36) was used. The exposure was measured by 16S rRNA sequencing (gut microbiome) and mediator by targeted metabolomics (sphingolipids). Dimensionality reduction was achieved by principle component analysis and Shannon diversity. Cox regression and procrustes analyses were used to assess the association between gut microbiome and T2D and sphingolipids and T2D, and between gut microbiome and sphingolipids, respectively. Mediation was tested familywise using mediation analysis with permutation testing and Bonferroni correction.</p><p><strong>Results: </strong>Our study confirmed associations between gut microbiome and T2D and sphingolipids and T2D. Additionally, we showed that the gut microbiome was associated with sphingolipids. The association between gut microbiome and T2D was partly mediated by a sphingolipid principal component, which represents a dominance of ceramide species over more complex sphingolipids (HR 1.17; 95% CI 1.08 to 1.28; proportional explained 48%), and by Shannon diversity (HR 0.97; 95% CI 0.95 to 0.99; proportional explained 24.8%).</p><p><strong>Conclusions: </strong>These data suggest that sphingolipids mediate the association between microbiome and T2D risk. 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Plasma sphingolipids mediate the association between gut microbiome composition and type 2 diabetes risk in the HELIUS cohort: a case-cohort study.
Introduction: The association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether sphingolipids mediate the association between gut microbiome and T2D, using data from the Healthy Life in an Urban Setting study.
Research design and methods: Participants were of Dutch or South-Asian Surinamese ethnicity, aged 18-70 years, and without T2D at baseline. A case-cohort design (subcohort n=176, cases incident T2D n=36) was used. The exposure was measured by 16S rRNA sequencing (gut microbiome) and mediator by targeted metabolomics (sphingolipids). Dimensionality reduction was achieved by principle component analysis and Shannon diversity. Cox regression and procrustes analyses were used to assess the association between gut microbiome and T2D and sphingolipids and T2D, and between gut microbiome and sphingolipids, respectively. Mediation was tested familywise using mediation analysis with permutation testing and Bonferroni correction.
Results: Our study confirmed associations between gut microbiome and T2D and sphingolipids and T2D. Additionally, we showed that the gut microbiome was associated with sphingolipids. The association between gut microbiome and T2D was partly mediated by a sphingolipid principal component, which represents a dominance of ceramide species over more complex sphingolipids (HR 1.17; 95% CI 1.08 to 1.28; proportional explained 48%), and by Shannon diversity (HR 0.97; 95% CI 0.95 to 0.99; proportional explained 24.8%).
Conclusions: These data suggest that sphingolipids mediate the association between microbiome and T2D risk. Future research is needed to confirm observed findings and elucidate causality on a molecular level.
期刊介绍:
BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of
high-quality — and evidence-based — original research articles.