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; Göran Bergström; Suzan van der Meij; Bart A van Wagensveld; Joost B L Hoekstra; Frits Holleman; Erik S G Stroes; Albert K Groen; Fredrik Bäckhed; 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, Göran Bergström, Suzan van der Meij, Bart A van Wagensveld, Joost B L HoekstraFrits Holleman, Erik S G Stroes, Albert K Groen, Fredrik Bäckhed, 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.

Originalsprog	Engelsk
Tidsskrift	PloS one
Vol/bind	12
Udgave nummer	11
Sider (fra-til)	e0181693
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0181693
Status	Udgivet - nov. 2017

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ntestinal Ralstonia pickettii augments glucose intolerance in obesityForlagets udgivne version, 2,25 MBLicens: CC BY

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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., Bergström, G., van der Meij, S., van Wagensveld, B. A., ... Nieuwdorp, M. (2017). Intestinal Ralstonia pickettii augments glucose intolerance in obesity. PloS one, 12(11), e0181693. https://doi.org/10.1371/journal.pone.0181693

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, Bergström, G, van der Meij, S, van Wagensveld, BA, Hoekstra, JBL, Holleman, F, Stroes, ESG, Groen, AK, Bäckhed, F, de Vos, WM & Nieuwdorp, M 2017, 'Intestinal Ralstonia pickettii augments glucose intolerance in obesity', PloS one, bind 12, nr. 11, s. 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.",

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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 G{\"o}ran Bergstr{\"o}m 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 B{\"a}ckhed and {de Vos}, {Willem M} and Max Nieuwdorp",

year = "2017",

month = nov,

doi = "10.1371/journal.pone.0181693",

language = "English",

volume = "12",

pages = "e0181693",

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issn = "1932-6203",

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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 - Bergström, Göran

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 - Bäckhed, Fredrik

AU - de Vos, Willem M

AU - Nieuwdorp, Max

PY - 2017/11

Y1 - 2017/11

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 - Aged

KW - Animals

KW - DNA, Bacterial

KW - Diabetes Mellitus, Type 2

KW - Diet, High-Fat

KW - Feces

KW - Female

KW - Glucose Intolerance

KW - Gram-Negative Bacterial Infections

KW - Humans

KW - Inflammation

KW - Intestines

KW - Intra-Abdominal Fat

KW - Male

KW - Mice, Inbred C57BL

KW - Obesity

KW - Ralstonia pickettii

KW - Journal Article

U2 - 10.1371/journal.pone.0181693

DO - 10.1371/journal.pone.0181693

M3 - Journal article

C2 - 29166392

SN - 1932-6203

VL - 12

SP - e0181693

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 11

ER -

Intestinal Ralstonia pickettii augments glucose intolerance in obesity

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