Aberrant intestinal microbiota in individuals with prediabetes

Kristine Højgaard Allin; Valentina Tremaroli; Robert Caesar; Benjamin Anderschou Holbech Jensen; Mads Thue Fejerskov  Damgaard; Martin I Bahl; Tine R Licht; Tue Haldor Hansen; Trine Nielsen; Thomas M Dantoft; Allan Linneberg; Torben Jørgensen; Henrik Vestergaard; Karsten Kristiansen; Paul W. Franks; IMI-DIRECT consortium; Torben Hansen; Gert Fredrik Bäckhed; Oluf Borbye Pedersen

doi:10.1007/s00125-018-4550-1

Aberrant intestinal microbiota in individuals with prediabetes

Kristine Højgaard Allin, Valentina Tremaroli, Robert Caesar, Benjamin Anderschou Holbech Jensen, Mads Thue Fejerskov Damgaard, Martin I Bahl, Tine R Licht, Tue Haldor Hansen, Trine Nielsen, Thomas M Dantoft, Allan Linneberg, Torben Jørgensen, Henrik Vestergaard, Karsten Kristiansen, Paul W. Franks, IMI-DIRECT consortium, Torben Hansen, Gert Fredrik Bäckhed, Oluf Borbye Pedersen

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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.

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	61
Udgave nummer	4
Sider (fra-til)	810-820
Antal sider	11
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-018-4550-1
Status	Udgivet - 1 apr. 2018

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10.1007/s00125-018-4550-1Licens: CC BY

Aberrant intestinal microbiota in individuals with prediabetesForlagets udgivne version, 749 KBLicens: CC BY

Citationsformater

Allin, K. H., Tremaroli, V., Caesar, R., Jensen, B. A. H., Damgaard, M. T. F., Bahl, M. I., Licht, T. R., Hansen, T. H., Nielsen, T., Dantoft, T. M., Linneberg, A., Jørgensen, T., Vestergaard, H., Kristiansen, K., Franks, P. W., IMI-DIRECT consortium, Hansen, T., Bäckhed, G. F., & Pedersen, O. B. (2018). Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia, 61(4), 810-820. https://doi.org/10.1007/s00125-018-4550-1

Allin, KH, Tremaroli, V, Caesar, R, Jensen, BAH , Damgaard, MTF, Bahl, MI, Licht, TR, Hansen, TH, Nielsen, T, Dantoft, TM, Linneberg, A, Jørgensen, T, Vestergaard, H , Kristiansen, K, Franks, PW, IMI-DIRECT consortium, Hansen, T , Bäckhed, GF & Pedersen, OB 2018, 'Aberrant intestinal microbiota in individuals with prediabetes', Diabetologia, bind 61, nr. 4, s. 810-820. https://doi.org/10.1007/s00125-018-4550-1

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title = "Aberrant intestinal microbiota in individuals with prediabetes",

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.",

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author = "Allin, {Kristine H{\o}jgaard} and Valentina Tremaroli and Robert Caesar and Jensen, {Benjamin Anderschou Holbech} and Damgaard, {Mads Thue Fejerskov} and Bahl, {Martin I} and Licht, {Tine R} and Hansen, {Tue Haldor} and Trine Nielsen and Dantoft, {Thomas M} and Allan Linneberg and Torben J{\o}rgensen and Henrik Vestergaard and Karsten Kristiansen and Franks, {Paul W.} and {IMI-DIRECT consortium} and Torben Hansen and B{\"a}ckhed, {Gert Fredrik} and Pedersen, {Oluf Borbye}",

year = "2018",

month = apr,

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doi = "10.1007/s00125-018-4550-1",

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pages = "810--820",

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TY - JOUR

T1 - Aberrant intestinal microbiota in individuals with prediabetes

AU - Allin, Kristine Højgaard

AU - Tremaroli, Valentina

AU - Caesar, Robert

AU - Jensen, Benjamin Anderschou Holbech

AU - Damgaard, Mads Thue Fejerskov

AU - Bahl, Martin I

AU - Licht, Tine R

AU - Hansen, Tue Haldor

AU - Nielsen, Trine

AU - Dantoft, Thomas M

AU - Linneberg, Allan

AU - Jørgensen, Torben

AU - Vestergaard, Henrik

AU - Kristiansen, Karsten

AU - Franks, Paul W.

AU - IMI-DIRECT consortium

AU - Hansen, Torben

AU - Bäckhed, Gert Fredrik

AU - Pedersen, Oluf Borbye

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1007/s00125-018-4550-1

DO - 10.1007/s00125-018-4550-1

M3 - Journal article

C2 - 29379988

SN - 0012-186X

VL - 61

SP - 810

EP - 820

JO - Diabetologia

JF - Diabetologia

IS - 4

ER -

Aberrant intestinal microbiota in individuals with prediabetes

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