PMID- 29166392 OWN - NLM STAT- MEDLINE DCOM- 20171211 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 11 DP - 2017 TI - Intestinal Ralstonia pickettii augments glucose intolerance in obesity. PG - e0181693 LID - 10.1371/journal.pone.0181693 [doi] LID - e0181693 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. FAU - Udayappan, Shanthadevi D AU - Udayappan SD AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Kovatcheva-Datchary, Petia AU - Kovatcheva-Datchary P AD - Wallenberg Laboratory, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Bakker, Guido J AU - Bakker GJ AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Havik, Stefan R AU - Havik SR AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Herrema, Hilde AU - Herrema H AUID- ORCID: 0000-0002-0112-6348 AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Cani, Patrice D AU - Cani PD AD - Universite catholique de Louvain, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Louvain Drug Research Institute, Brussels, Belgium. FAU - Bouter, Kristien E AU - Bouter KE AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Belzer, Clara AU - Belzer C AD - Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands. FAU - Witjes, Julia J AU - Witjes JJ AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Vrieze, Anne AU - Vrieze A AD - Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - de Sonnaville, Eleanore Susanne Victoria AU - de Sonnaville ESV AD - Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Chaplin, Alice AU - Chaplin A AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - van Raalte, Daniel H AU - van Raalte DH AD - Diabetes Center, Department of Internal medicine, VU University Medical Center, Amsterdam, The Netherlands. AD - ICAR, VU University Medical Center, Amsterdam, The Netherlands. FAU - Aalvink, Steven AU - Aalvink S AD - Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands. FAU - Dallinga-Thie, Geesje M AU - Dallinga-Thie GM AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Heilig, Hans G H J AU - Heilig HGHJ AD - Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands. FAU - Bergstrom, Goran AU - Bergstrom G AD - Wallenberg Laboratory, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - van der Meij, Suzan AU - van der Meij S AD - Department of Surgery, Flevo Hospital, Almere, The Netherlands. FAU - van Wagensveld, Bart A AU - van Wagensveld BA AD - Department of Surgery, Sint Lucas Andreas Hospital, Amsterdam, The Netherlands. FAU - Hoekstra, Joost B L AU - Hoekstra JBL AD - Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Holleman, Frits AU - Holleman F AD - Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Stroes, Erik S G AU - Stroes ESG AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Groen, Albert K AU - Groen AK AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. AD - Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Backhed, Fredrik AU - Backhed F AD - Wallenberg Laboratory, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - de Vos, Willem M AU - de Vos WM AD - Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands. AD - RPU Immunobiology, University of Helsinki, Helsinki, Finland. FAU - Nieuwdorp, Max AU - Nieuwdorp M AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. AD - Wallenberg Laboratory, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. AD - Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. AD - Diabetes Center, Department of Internal medicine, VU University Medical Center, Amsterdam, The Netherlands. AD - ICAR, VU University Medical Center, Amsterdam, The Netherlands. LA - eng PT - Journal Article DEP - 20171122 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (DNA, Bacterial) SB - IM EIN - PLoS One. 2018 Jan 30;13(1):e0192339. PMID: 29381738 MH - Aged MH - Animals MH - DNA, Bacterial/analysis MH - Diabetes Mellitus, Type 2/complications/microbiology MH - Diet, High-Fat MH - Feces/microbiology MH - Female MH - Glucose Intolerance/*complications/*microbiology MH - Gram-Negative Bacterial Infections/*microbiology/pathology MH - Humans MH - Inflammation/complications/pathology MH - Intestines/*microbiology/pathology MH - Intra-Abdominal Fat/microbiology/pathology MH - Male MH - Mice, Inbred C57BL MH - Obesity/*complications/*microbiology MH - Ralstonia pickettii/*physiology PMC - PMC5699813 COIS- Competing Interests: We have the following interests. This study was partly funded by AFA insurances. M.N. and W.M.deV. are founders, own equity and are in the Scientific Advisory Board of Caelus Pharmaceuticals, the Netherlands; WMdV is in the Scientific Advisory Board of Chr Hansen Horsholm Danmark and the M.N. and W.M.deV. are founders, own equity and are in the Scientific Advisory Board of Caelus Pharmaceutical(NIHS) Lausanne Switzerland. F.B. is a founder of MetaboGen AB, Sweden. F.B. and G.B own equity in MetaboGen AB, Sweden. None of these are directly relevant to the current paper. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. EDAT- 2017/11/23 06:00 MHDA- 2017/12/12 06:00 PMCR- 2017/11/22 CRDT- 2017/11/23 06:00 PHST- 2017/01/13 00:00 [received] PHST- 2017/07/04 00:00 [accepted] PHST- 2017/11/23 06:00 [entrez] PHST- 2017/11/23 06:00 [pubmed] PHST- 2017/12/12 06:00 [medline] PHST- 2017/11/22 00:00 [pmc-release] AID - PONE-D-17-01669 [pii] AID - 10.1371/journal.pone.0181693 [doi] PST - epublish SO - PLoS One. 2017 Nov 22;12(11):e0181693. doi: 10.1371/journal.pone.0181693. eCollection 2017.