Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study

Pieter F. de Groot; Clara Belzer; Omrum Aydin; Evgeni Levin; Johannes H. Levels; Steven Aalvink; Fransje Boot; Frits Holleman; Daniel H. van Raalte; Torsten P. Scheithauer; Suat Simsek; Frank G. Schaap; Steven W. M. Olde Damink; Bart O. Roep; Joost B. Hoekstra; Willem M. de Vos; Max Nieuwdorp

doi:10.1371/journal.pone.0188475

Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study

Pieter F. de Groot^*, Clara Belzer, Omrum Aydin, Evgeni Levin, Johannes H. Levels, Steven Aalvink, Fransje Boot, Frits Holleman, Daniel H. van Raalte, Torsten P. Scheithauer, Suat Simsek, Frank G. Schaap, Steven W. M. Olde Damink, Bart O. Roep, Joost B. Hoekstra, Willem M. de Vos, Max Nieuwdorp^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective

Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking.

Research design and methods

We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured.

Results

Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA.

Conclusions

We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.

Original language	English
Article number	0188475
Number of pages	14
Journal	PLOS ONE
Volume	12
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0188475
Publication status	Published - 6 Dec 2017

Keywords

CHAIN FATTY-ACIDS
ANTIISLET CELL AUTOIMMUNITY
GUT MICROBIOME
CHILDREN
SUSCEPTIBILITY
CONTRIBUTES
SELECTION
BACTERIA
MELLITUS
DISEASES

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Cite this

de Groot, P. F., Belzer, C., Aydin, O., Levin, E., Levels, J. H., Aalvink, S., Boot, F., Holleman, F., van Raalte, D. H., Scheithauer, T. P., Simsek, S., Schaap, F. G., Damink, S. W. M. O., Roep, B. O., Hoekstra, J. B., de Vos, W. M., & Nieuwdorp, M. (2017). Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. PLOS ONE, 12(12), Article 0188475. https://doi.org/10.1371/journal.pone.0188475

@article{2d4b9bac676546408796d70b75671e18,

title = "Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study",

abstract = "ObjectiveEnvironmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking.Research design and methodsWe included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured.ResultsOral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA.ConclusionsWe conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.",

keywords = "CHAIN FATTY-ACIDS, ANTIISLET CELL AUTOIMMUNITY, GUT MICROBIOME, CHILDREN, SUSCEPTIBILITY, CONTRIBUTES, SELECTION, BACTERIA, MELLITUS, DISEASES",

author = "{de Groot}, {Pieter F.} and Clara Belzer and Omrum Aydin and Evgeni Levin and Levels, {Johannes H.} and Steven Aalvink and Fransje Boot and Frits Holleman and {van Raalte}, {Daniel H.} and Scheithauer, {Torsten P.} and Suat Simsek and Schaap, {Frank G.} and Damink, {Steven W. M. Olde} and Roep, {Bart O.} and Hoekstra, {Joost B.} and {de Vos}, {Willem M.} and Max Nieuwdorp",

year = "2017",

month = dec,

day = "6",

doi = "10.1371/journal.pone.0188475",

language = "English",

volume = "12",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "12",

}

de Groot, PF, Belzer, C, Aydin, O, Levin, E, Levels, JH, Aalvink, S, Boot, F, Holleman, F, van Raalte, DH, Scheithauer, TP, Simsek, S, Schaap, FG , Damink, SWMO, Roep, BO, Hoekstra, JB, de Vos, WM & Nieuwdorp, M 2017, 'Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study', PLOS ONE, vol. 12, no. 12, 0188475. https://doi.org/10.1371/journal.pone.0188475

TY - JOUR

T1 - Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study

AU - de Groot, Pieter F.

AU - Belzer, Clara

AU - Aydin, Omrum

AU - Levin, Evgeni

AU - Levels, Johannes H.

AU - Aalvink, Steven

AU - Boot, Fransje

AU - Holleman, Frits

AU - van Raalte, Daniel H.

AU - Scheithauer, Torsten P.

AU - Simsek, Suat

AU - Schaap, Frank G.

AU - Damink, Steven W. M. Olde

AU - Roep, Bart O.

AU - Hoekstra, Joost B.

AU - de Vos, Willem M.

AU - Nieuwdorp, Max

PY - 2017/12/6

Y1 - 2017/12/6

N2 - ObjectiveEnvironmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking.Research design and methodsWe included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured.ResultsOral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA.ConclusionsWe conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.

AB - ObjectiveEnvironmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking.Research design and methodsWe included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured.ResultsOral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA.ConclusionsWe conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.

KW - CHAIN FATTY-ACIDS

KW - ANTIISLET CELL AUTOIMMUNITY

KW - GUT MICROBIOME

KW - CHILDREN

KW - SUSCEPTIBILITY

KW - CONTRIBUTES

KW - SELECTION

KW - BACTERIA

KW - MELLITUS

KW - DISEASES

U2 - 10.1371/journal.pone.0188475

DO - 10.1371/journal.pone.0188475

M3 - Article

C2 - 29211757

SN - 1932-6203

VL - 12

JO - PLOS ONE

JF - PLOS ONE

IS - 12

M1 - 0188475

ER -