Aberrant intestinal microbiota in individuals with prediabetes

Kristine H. Allin*, Valentina Tremaroli, Robert Caesar, Benjamin A.H. Jensen, Mads T.F. Damgaard, Martin Iain Bahl, Tine Rask Licht, Tue H. Hansen, Trine Nielsen, Thomas M. Dantoft, Allan Linneberg, Torben Jørgensen, Henrik Vestergaard, Karsten Kristiansen, Paul W. Franks, Torben Hansen, Fredrik Bäckhed, Oluf Pedersen, the IMI-DIRECT consortium

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

135 Downloads (Pure)

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

Original languageEnglish
JournalDiabetologia
Volume61
Issue number4
Pages (from-to)810-820
ISSN0012-186X
DOIs
Publication statusPublished - 29 Jan 2018

Keywords

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

Cite this

Allin, K. H., Tremaroli, V., Caesar, R., Jensen, B. A. H., Damgaard, M. T. F., Bahl, M. I., ... the IMI-DIRECT consortium (2018). Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia, 61(4), 810-820. https://doi.org/10.1007/s00125-018-4550-1
Allin, Kristine H. ; Tremaroli, Valentina ; Caesar, Robert ; Jensen, Benjamin A.H. ; Damgaard, Mads T.F. ; Bahl, Martin Iain ; Rask Licht, Tine ; Hansen, Tue H. ; Nielsen, Trine ; Dantoft, Thomas M. ; Linneberg, Allan ; Jørgensen, Torben ; Vestergaard, Henrik ; Kristiansen, Karsten ; Franks, Paul W. ; Hansen, Torben ; Bäckhed, Fredrik ; Pedersen, Oluf ; the IMI-DIRECT consortium. / Aberrant intestinal microbiota in individuals with prediabetes. In: Diabetologia. 2018 ; Vol. 61, No. 4. pp. 810-820.
@article{a6325e80a9034c6dbc38632063971409,
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), padj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), padj = 5 × 10−4; 0.51 (SEM 0.11), padj = 1 × 10−4; 0.60 (SEM 0.21), padj = 0.0497; and 0.92 (SEM 0.21), padj = 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), padj = 2 × 10−3 and −1.65 (SEM 0.34), padj = 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",
author = "Allin, {Kristine H.} and Valentina Tremaroli and Robert Caesar and Jensen, {Benjamin A.H.} and Damgaard, {Mads T.F.} and Bahl, {Martin Iain} and {Rask Licht}, Tine and Hansen, {Tue H.} 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 Torben Hansen and Fredrik B{\"a}ckhed and Oluf Pedersen and {the IMI-DIRECT consortium}",
year = "2018",
month = "1",
day = "29",
doi = "10.1007/s00125-018-4550-1",
language = "English",
volume = "61",
pages = "810--820",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "4",

}

Allin, KH, Tremaroli, V, Caesar, R, Jensen, BAH, Damgaard, MTF, Bahl, MI, Rask Licht, T, Hansen, TH, Nielsen, T, Dantoft, TM, Linneberg, A, Jørgensen, T, Vestergaard, H, Kristiansen, K, Franks, PW, Hansen, T, Bäckhed, F, Pedersen, O & the IMI-DIRECT consortium 2018, 'Aberrant intestinal microbiota in individuals with prediabetes', Diabetologia, vol. 61, no. 4, pp. 810-820. https://doi.org/10.1007/s00125-018-4550-1

Aberrant intestinal microbiota in individuals with prediabetes. / Allin, Kristine H.; Tremaroli, Valentina; Caesar, Robert; Jensen, Benjamin A.H.; Damgaard, Mads T.F.; Bahl, Martin Iain; Rask Licht, Tine ; Hansen, Tue H.; Nielsen, Trine; Dantoft, Thomas M.; Linneberg, Allan; Jørgensen, Torben; Vestergaard, Henrik; Kristiansen, Karsten; Franks, Paul W.; Hansen, Torben; Bäckhed, Fredrik; Pedersen, Oluf; the IMI-DIRECT consortium.

In: Diabetologia, Vol. 61, No. 4, 29.01.2018, p. 810-820.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Aberrant intestinal microbiota in individuals with prediabetes

AU - Allin, Kristine H.

AU - Tremaroli, Valentina

AU - Caesar, Robert

AU - Jensen, Benjamin A.H.

AU - Damgaard, Mads T.F.

AU - Bahl, Martin Iain

AU - Rask Licht, Tine

AU - Hansen, Tue H.

AU - Nielsen, Trine

AU - Dantoft, Thomas M.

AU - Linneberg, Allan

AU - Jørgensen, Torben

AU - Vestergaard, Henrik

AU - Kristiansen, Karsten

AU - Franks, Paul W.

AU - Hansen, Torben

AU - Bäckhed, Fredrik

AU - Pedersen, Oluf

AU - the IMI-DIRECT consortium

PY - 2018/1/29

Y1 - 2018/1/29

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), padj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), padj = 5 × 10−4; 0.51 (SEM 0.11), padj = 1 × 10−4; 0.60 (SEM 0.21), padj = 0.0497; and 0.92 (SEM 0.21), padj = 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), padj = 2 × 10−3 and −1.65 (SEM 0.34), padj = 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), padj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), padj = 5 × 10−4; 0.51 (SEM 0.11), padj = 1 × 10−4; 0.60 (SEM 0.21), padj = 0.0497; and 0.92 (SEM 0.21), padj = 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), padj = 2 × 10−3 and −1.65 (SEM 0.34), padj = 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 - Akkermansia muciniphila

KW - Clostridium

KW - Faecal transfer

KW - Gut microbiota

KW - Hyperglycaemia

KW - Intestinal microbiota

KW - Low-grade inflammation

KW - Prediabetes

U2 - 10.1007/s00125-018-4550-1

DO - 10.1007/s00125-018-4550-1

M3 - Journal article

C2 - 29379988

AN - SCOPUS:85041137334

VL - 61

SP - 810

EP - 820

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 4

ER -

Allin KH, Tremaroli V, Caesar R, Jensen BAH, Damgaard MTF, Bahl MI et al. Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia. 2018 Jan 29;61(4):810-820. https://doi.org/10.1007/s00125-018-4550-1