title: Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals.
abstract: The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigated the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism.
  
  
  
  We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m2) prediabetic men and women (ages, 45-70 y) from October 2014 through October 2015 in Maastricht, The Netherlands. The participants were assigned randomly to groups who ingested 15 g GOS or isocaloric placebo (maltodextrin) daily with their regular meals for 12 weeks. Before and after this period, we collected data on peripheral and adipose tissue insulin sensitivity, fecal microbiota composition, plasma and fecal SCFA, energy expenditure and substrate oxidation, body composition, and hormonal and inflammatory responses. The primary outcome was the effect of GOS on peripheral insulin sensitivity, measured by the hyperinsulinemic-euglycemic clamp method.
  
  
  
  Supplementation of diets with GOS, but not placebo, increased the abundance of Bifidobacterium species in feces by 5-fold (P = .009; q = 0.144). Microbial richness or diversity in fecal samples were not affected. We did not observe any differences in fecal or fasting plasma SCFA concentrations or in systemic concentrations of gut-derived hormones, incretins, lipopolysaccharide-binding protein, or other markers of inflammation. In addition, no significant alterations in peripheral and adipose tissue insulin sensitivity, body composition, and energy and substrate metabolism were found.
  
  
  
  Twelve-week supplementation of GOS selectively increased fecal Bifidobacterium species abundance, but this did not produce significant changes in insulin sensitivity or related substrate and energy metabolism in overweight or obese prediabetic men and women. ClincialTrials.gov number, NCT02271776.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands. Electronic address: Emanuel.canfora@maastrichtuniversity.nl.
authors.forename: Emanuel E
authors.initials: EE
authors.lastname: Canfora
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Christina M
authors.initials: CM
authors.lastname: van der Beek
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Gerben D A
authors.initials: GDA
authors.lastname: Hermes
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Goossens
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Johan W E
authors.initials: JWE
authors.lastname: Jocken
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Hans M
authors.initials: HM
authors.lastname: van Eijk
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Beneficial Microbes Consultancy, Wageningen, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Venema
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Hauke
authors.initials: H
authors.lastname: Smidt
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Zoetendal
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Surgery, Universitätsklinikum Aachen, Aachen, Germany.
authors.forename: Cornelis H C
authors.initials: CHC
authors.lastname: Dejong
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Kaatje
authors.initials: K
authors.lastname: Lenaerts
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D019342:Acetic Acid / Q000032:analysis; D000209:Acute-Phase Proteins; D050154:Adiposity; D000368:Aged; D001644:Bifidobacterium; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002352:Carrier Proteins / Q000097:blood; D016207:Cytokines / Q000097:blood; D004269:DNA, Bacterial / Q000032:analysis*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004734:Energy Metabolism; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D005690:Galactose / Q000008:administration & dosage*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D009844:Oligosaccharides / Q000008:administration & dosage*; D011236:Prediabetic State / Q000150:complications / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D019342:Acetic Acid; D000209:Acute-Phase Proteins; D001786:Blood Glucose; D002352:Carrier Proteins; D016207:Cytokines; D004269:DNA, Bacterial; D005690:Galactose; D054795:Incretins; D007328:Insulin; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D000099231:Lipopolysaccharide-Binding Protein
keywords: Metabolic Control; Microbial Obesity; Prebiotics; Short-Chain Fatty Acids