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Aberrant intestinal microbiota in individuals with prediabetes

Journal article
Authors K. H. Allin
V. Tremaroli
Robert Caesar
B. A. H. Jensen
M. T. F. Damgaard
M. I. Bahl
T. R. Licht
T. H. Hansen
T. Nielsen
T. M. Dantoft
A. Linneberg
T. Jorgensen
H. Vestergaard
K. Kristiansen
P. W. Franks
T. Hansen
Fredrik Bäckhed
O. Pedersen
Published in Diabetologia
Volume 61
Issue 4
Pages 810-820
ISSN 0012-186X
Publication year 2018
Published at Wallenberg Laboratory
Center for Cardiovascular and Metabolic Research (CMR)
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 810-820
Language en
Links https://doi.org/10.1007/s00125-018-...
Keywords Akkermansia muciniphila, Clostridium, Faecal transfer, Gut microbiota, Hyperglycaemia, Intestinal, human gut microbiome, akkermansia-muciniphila, type-2, metformin, obesity, metagenome, bacteria, health, cohort, mucin, Endocrinology & Metabolism
Subject categories Endocrinology and Diabetes

Abstract

Aims/hypothesis Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA(1c) of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health. Methods In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age-and sex-matched individuals with normal glucose regulation. Results We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log(2) fold change -0.64 (SEM 0.23), p(adj) = 0.0497), whereas the abundances of Dorea, [ Ruminococcus], Sutterella and Streptococcus were increased (mean log(2) fold change 0.51 (SEM 0.12), p(adj) = 5 x 10(-4); 0.51 (SEM 0.11), p(adj) = 1 x 10-4; 0.60 (SEM 0.21), p(adj) = 0.0497; and 0.92 (SEM0.21), padj = 4 x 10(-4), respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log(2) fold change -1.74 (SEM0.41), p(adj) = 2 x 10(-3) and -1.65 (SEM0.34), p(adj) = 4 x 10(-4), respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice. Conclusions/interpretation Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

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