Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity
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Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. / Vrieze, Anne; Out, Carolien; Fuentes, Susana; Jonker, Lisanne; Reuling, Isaie; Kootte, Ruud S; van Nood, Els; Holleman, Frits; Knaapen, Max; Romijn, Johannes A; Soeters, Maarten R; Blaak, Ellen E; Dallinga-Thie, Geesje M; Reijnders, Dorien; Ackermans, Mariëtte T; Serlie, Mireille J; Knop, Filip K; Holst, Jens Juul; van der Ley, Claude; Kema, Ido P; Zoetendal, Erwin G; de Vos, Willem M; Hoekstra, Joost B L; Stroes, Erik S; Groen, Albert K; Nieuwdorp, Max.
In: Journal of Hepatology, Vol. 60, No. 4, 04.2014, p. 824-31.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity
AU - Vrieze, Anne
AU - Out, Carolien
AU - Fuentes, Susana
AU - Jonker, Lisanne
AU - Reuling, Isaie
AU - Kootte, Ruud S
AU - van Nood, Els
AU - Holleman, Frits
AU - Knaapen, Max
AU - Romijn, Johannes A
AU - Soeters, Maarten R
AU - Blaak, Ellen E
AU - Dallinga-Thie, Geesje M
AU - Reijnders, Dorien
AU - Ackermans, Mariëtte T
AU - Serlie, Mireille J
AU - Knop, Filip K
AU - Holst, Jens Juul
AU - van der Ley, Claude
AU - Kema, Ido P
AU - Zoetendal, Erwin G
AU - de Vos, Willem M
AU - Hoekstra, Joost B L
AU - Stroes, Erik S
AU - Groen, Albert K
AU - Nieuwdorp, Max
N1 - Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2014/4
Y1 - 2014/4
N2 - BACKGROUND & AIMS: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism.METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured.RESULTS: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters.CONCLUSIONS: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566).
AB - BACKGROUND & AIMS: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism.METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured.RESULTS: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters.CONCLUSIONS: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566).
U2 - 10.1016/j.jhep.2013.11.034
DO - 10.1016/j.jhep.2013.11.034
M3 - Journal article
C2 - 24316517
VL - 60
SP - 824
EP - 831
JO - Journal of Hepatology, Supplement
JF - Journal of Hepatology, Supplement
SN - 0169-5185
IS - 4
ER -
ID: 117854465