Intestinal Ralstonia pickettii augments glucose intolerance in obesity

Shanthadevi D. Udayappan; Petia Kovatcheva-Datchary; Guido J. Bakker; Stefan R. Havik; Hilde Herrema; Patrice D. Cani; Kristien E. Bouter; Clara Belzer; Julia J. Witjes; Anne Vrieze; Noor de Sonnaville; Alice Chaplin; Daniel H. van Raalte; Steven Aalvink; Geesje M. Dallinga-Thie; Hans G. H. J. Heilig; Goran Bergstrom; Suzan van der Meij; Bart A. van Wagensveld; Joost B. L. Hoekstra; Frits Holleman; Erik S. G. Stroes; Albert K. Groen; Fredrik Backhed; Willem M. de Vos; Max Nieuwdorp

doi:10.1371/journal.pone.0181693

Intestinal Ralstonia pickettii augments glucose intolerance in obesity

Shanthadevi D. Udayappan, Petia Kovatcheva-Datchary, Guido J. Bakker, Stefan R. Havik, Hilde Herrema, Patrice D. Cani, Kristien E. Bouter, Clara Belzer, Julia J. Witjes, Anne Vrieze, Noor de Sonnaville, Alice Chaplin, Daniel H. van Raalte, Steven Aalvink, Geesje M. Dallinga-Thie, Hans G. H. J. Heilig, Goran Bergstrom, Suzan van der Meij, Bart A. van Wagensveld, Joost B. L. HoekstraFrits Holleman, Erik S. G. Stroes, Albert K. Groen, Fredrik Backhed, Willem M. de Vos, Max Nieuwdorp

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Abstract

An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.

Original language	English
Article number	e0181693
Number of pages	15
Journal	PLoS ONE
Volume	12
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0181693
Publication status	Published - 22-Nov-2017

Keywords

LOW-GRADE INFLAMMATION
DIET-INDUCED OBESITY
METABOLIC SYNDROME
INSULIN-RESISTANCE
GUT MICROBIOTA
GASTROINTESTINAL-TRACT
RECEPTOR 5
FAT
IMMUNITY
BACTERIA

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Udayappan, S. (Creator), Kovatcheva-Datchary, P. (Creator), Bakker, G. J. (Creator), Havik, S. R. (Creator), Herrema, H. (Creator), Cani, P. D. (Creator), Bouter, K. E. (Creator), Belzer, C. (Creator), Witjes, J. J. (Creator), Vrieze, A. (Creator), de Sonnaville, N. (Creator), Chaplin-Scott, A. (Creator), van Raalte, D. H. (Creator), Aalvink, S. (Creator), Dallinga-Thie, G. (Creator), Heilig, H. G. H. J. (Creator), Bergstrom, G. (Creator), van der Meij, S. (Creator), van Wagensveld, B. A. (Creator), Hoekstra, J. B. L. (Creator), Holleman, F. (Creator), Stroes, E. S. G. (Creator), Groen, A. (Creator), Backhed, F. (Creator), de Vos, W. M. (Creator) & Nieuwdorp, M. (Creator), University of Groningen, 1-Dec-2017
DOI: 10.5061/dryad.q5s51
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Udayappan, S. D., Kovatcheva-Datchary, P., Bakker, G. J., Havik, S. R., Herrema, H., Cani, P. D., Bouter, K. E., Belzer, C., Witjes, J. J., Vrieze, A., de Sonnaville, N., Chaplin, A., van Raalte, D. H., Aalvink, S., Dallinga-Thie, G. M., Heilig, H. G. H. J., Bergstrom, G., van der Meij, S., van Wagensveld, B. A., ... Nieuwdorp, M. (2017). Intestinal Ralstonia pickettii augments glucose intolerance in obesity. PLoS ONE, 12(11), Article e0181693. https://doi.org/10.1371/journal.pone.0181693

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title = "Intestinal Ralstonia pickettii augments glucose intolerance in obesity",

abstract = "An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.",

keywords = "LOW-GRADE INFLAMMATION, DIET-INDUCED OBESITY, METABOLIC SYNDROME, INSULIN-RESISTANCE, GUT MICROBIOTA, GASTROINTESTINAL-TRACT, RECEPTOR 5, FAT, IMMUNITY, BACTERIA",

author = "Udayappan, {Shanthadevi D.} and Petia Kovatcheva-Datchary and Bakker, {Guido J.} and Havik, {Stefan R.} and Hilde Herrema and Cani, {Patrice D.} and Bouter, {Kristien E.} and Clara Belzer and Witjes, {Julia J.} and Anne Vrieze and {de Sonnaville}, Noor and Alice Chaplin and {van Raalte}, {Daniel H.} and Steven Aalvink and Dallinga-Thie, {Geesje M.} and Heilig, {Hans G. H. J.} and Goran Bergstrom and {van der Meij}, Suzan and {van Wagensveld}, {Bart A.} and Hoekstra, {Joost B. L.} and Frits Holleman and Stroes, {Erik S. G.} and Groen, {Albert K.} and Fredrik Backhed and {de Vos}, {Willem M.} and Max Nieuwdorp",

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Udayappan, SD, Kovatcheva-Datchary, P, Bakker, GJ, Havik, SR, Herrema, H, Cani, PD, Bouter, KE, Belzer, C, Witjes, JJ, Vrieze, A, de Sonnaville, N, Chaplin, A, van Raalte, DH, Aalvink, S, Dallinga-Thie, GM, Heilig, HGHJ, Bergstrom, G, van der Meij, S, van Wagensveld, BA, Hoekstra, JBL, Holleman, F, Stroes, ESG, Groen, AK, Backhed, F, de Vos, WM & Nieuwdorp, M 2017, 'Intestinal Ralstonia pickettii augments glucose intolerance in obesity', PLoS ONE, vol. 12, no. 11, e0181693. https://doi.org/10.1371/journal.pone.0181693

TY - JOUR

T1 - Intestinal Ralstonia pickettii augments glucose intolerance in obesity

AU - Udayappan, Shanthadevi D.

AU - Kovatcheva-Datchary, Petia

AU - Bakker, Guido J.

AU - Havik, Stefan R.

AU - Herrema, Hilde

AU - Cani, Patrice D.

AU - Bouter, Kristien E.

AU - Belzer, Clara

AU - Witjes, Julia J.

AU - Vrieze, Anne

AU - de Sonnaville, Noor

AU - Chaplin, Alice

AU - van Raalte, Daniel H.

AU - Aalvink, Steven

AU - Dallinga-Thie, Geesje M.

AU - Heilig, Hans G. H. J.

AU - Bergstrom, Goran

AU - van der Meij, Suzan

AU - van Wagensveld, Bart A.

AU - Hoekstra, Joost B. L.

AU - Holleman, Frits

AU - Stroes, Erik S. G.

AU - Groen, Albert K.

AU - Backhed, Fredrik

AU - de Vos, Willem M.

AU - Nieuwdorp, Max

PY - 2017/11/22

Y1 - 2017/11/22

N2 - An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.

AB - An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.

KW - LOW-GRADE INFLAMMATION

KW - DIET-INDUCED OBESITY

KW - METABOLIC SYNDROME

KW - INSULIN-RESISTANCE

KW - GUT MICROBIOTA

KW - GASTROINTESTINAL-TRACT

KW - RECEPTOR 5

KW - FAT

KW - IMMUNITY

KW - BACTERIA

U2 - 10.1371/journal.pone.0181693

DO - 10.1371/journal.pone.0181693

M3 - Article

C2 - 29166392

SN - 1932-6203

VL - 12

JO - PLoS ONE

JF - PLoS ONE

IS - 11

M1 - e0181693

ER -

Intestinal Ralstonia pickettii augments glucose intolerance in obesity

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