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Diabetologia. 2018 Apr;61(4):810-820. doi: 10.1007/s00125-018-4550-1. Epub 2018 Jan 29.

Aberrant intestinal microbiota in individuals with prediabetes.

Author information

1
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark. kristine.allin@regionh.dk.
2
Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospital, the Capital Region, Copenhagen, Denmark. kristine.allin@regionh.dk.
3
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45, Gothenburg, Sweden. Valentina.Tremaroli@wlab.gu.se.
4
Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden. Valentina.Tremaroli@wlab.gu.se.
5
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45, Gothenburg, Sweden.
6
Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
7
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
8
National Food Institute, Technical University of Denmark, Lyngby, Denmark.
9
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
10
Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark.
11
Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
12
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
13
Faculty of Medicine, Aalborg University, Aalborg, Denmark.
14
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
15
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
16
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
17
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
18
Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
19
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
20
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark. oluf@sund.ku.dk.
21
Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark. oluf@sund.ku.dk.

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 HbA1c 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 log2 fold change -0.64 (SEM 0.23), p adj  = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), p adj  = 5 × 10-4; 0.51 (SEM 0.11), p adj  = 1 × 10-4; 0.60 (SEM 0.21), p adj  = 0.0497; and 0.92 (SEM 0.21), p adj  = 4 × 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 log2 fold change -1.74 (SEM 0.41), p adj  = 2 × 10-3 and -1.65 (SEM 0.34), p adj  = 4 × 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.

KEYWORDS:

Akkermansia muciniphila; Clostridium; Faecal transfer; Gut microbiota; Hyperglycaemia; Intestinal microbiota; Low-grade inflammation; Prediabetes

PMID:
29379988
DOI:
10.1007/s00125-018-4550-1
[Indexed for MEDLINE]

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