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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Article numbere0181693
JournalPLoS ONE
Volume12
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

Udayappan, S. D., Kovatcheva-Datchary, P., Bakker, G. J., Havik, S. R., Herrema, H., Cani, P. D., ... Nieuwdorp, M. (2017). Intestinal Ralstonia pickettii augments glucose intolerance in obesity. PLoS ONE, 12(11), [e0181693]. https://doi.org/10.1371/journal.pone.0181693