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A Fecal Metabolite ...
A Fecal Metabolite Signature of Impaired Fasting Glucose : Results From Two Independent Population-Based Cohorts
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- Nogal, Ana (author)
- St Thomas' Hospital
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- Tettamanzi, Francesca (author)
- St Thomas' Hospital
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- Dong, Qiuling (author)
- Helmholtz Zentrum München
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- Louca, Panayiotis (author)
- St Thomas' Hospital
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- Visconti, Alessia (author)
- St Thomas' Hospital
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- Christiansen, Colette (author)
- St Thomas' Hospital
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- Breuninger, Taylor (author)
- University of Augsburg
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- Linseisen, Jakob (author)
- University of Augsburg
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- Grallert, Harald (author)
- Helmholtz Zentrum München
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- Wawro, Nina (author)
- University of Augsburg
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- Asnicar, Francesco (author)
- University of Trento
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- Wong, Kari (author)
- Metabolon Inc.
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- Baleanu, Andrei Florin (author)
- St Thomas' Hospital
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- Michelotti, Gregory A. (author)
- Metabolon Inc.
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- Segata, Nicola (author)
- University of Trento
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- Falchi, Mario (author)
- St Thomas' Hospital
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- Peters, Annette (author)
- Helmholtz Zentrum München
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- Franks, Paul W. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Bagnardi, Vincenzo (author)
- University of Milano-Bicocca
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- Spector, Tim D. (author)
- St Thomas' Hospital
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- Bell, Jordana T. (author)
- St Thomas' Hospital
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- Gieger, Christian (author)
- Helmholtz Zentrum München
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- Valdes, Ana M. (author)
- University of Nottingham
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- Menni, Cristina (author)
- St Thomas' Hospital
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(creator_code:org_t)
- 2023
- 2023
- English 11 s.
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In: Diabetes. - 0012-1797. ; 72:12, s. 1870-1880
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Abstract
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- Prediabetes is a metabolic condition associated with gut mi-crobiome composition, although mechanisms remain elu-sive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicoti-nate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02–5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16–1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97–8], P = 0.0002). Although these are host-produced me-tabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- ref (subject category)
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Diabetes
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- By the author/editor
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Nogal, Ana
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Tettamanzi, Fran ...
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Dong, Qiuling
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Louca, Panayioti ...
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Visconti, Alessi ...
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Christiansen, Co ...
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Breuninger, Tayl ...
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Linseisen, Jakob
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Grallert, Harald
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Wawro, Nina
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Asnicar, Frances ...
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Wong, Kari
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Baleanu, Andrei ...
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Michelotti, Greg ...
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Segata, Nicola
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Falchi, Mario
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Peters, Annette
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Franks, Paul W.
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Bagnardi, Vincen ...
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Spector, Tim D.
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Bell, Jordana T.
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Gieger, Christia ...
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Valdes, Ana M.
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Menni, Cristina
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Diabetes
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Lund University