A Fecal Metabolite Signature of Impaired Fasting Glucose : Results From Two Independent Population-Based Cohorts
(2023) In Diabetes 72(12). p.1870-1880- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 72
- issue
- 12
- pages
- 11 pages
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:37699401
- scopus:85178291423
- ISSN
- 0012-1797
- DOI
- 10.2337/db23-0170
- language
- English
- LU publication?
- yes
- id
- ba38912a-bab3-44f1-b054-36271998a071
- date added to LUP
- 2023-12-29 09:59:50
- date last changed
- 2025-04-14 02:47:05
@article{ba38912a-bab3-44f1-b054-36271998a071,
abstract = {{<p>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.</p>}},
author = {{Nogal, Ana and Tettamanzi, Francesca and Dong, Qiuling and Louca, Panayiotis and Visconti, Alessia and Christiansen, Colette and Breuninger, Taylor and Linseisen, Jakob and Grallert, Harald and Wawro, Nina and Asnicar, Francesco and Wong, Kari and Baleanu, Andrei Florin and Michelotti, Gregory A. and Segata, Nicola and Falchi, Mario and Peters, Annette and Franks, Paul W. and Bagnardi, Vincenzo and Spector, Tim D. and Bell, Jordana T. and Gieger, Christian and Valdes, Ana M. and Menni, Cristina}},
issn = {{0012-1797}},
language = {{eng}},
number = {{12}},
pages = {{1870--1880}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{A Fecal Metabolite Signature of Impaired Fasting Glucose : Results From Two Independent Population-Based Cohorts}},
url = {{http://dx.doi.org/10.2337/db23-0170}},
doi = {{10.2337/db23-0170}},
volume = {{72}},
year = {{2023}},
}