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 - 2017/11/1
Y1 - 2017/11/1
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
UR - http://www.scopus.com/inward/record.url?scp=85034833566&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pone.0181693
DO - https://doi.org/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 -