Host-microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

TY - JOUR

T1 - Host-microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

AU - Molinaro, Antonio

AU - Caesar, Robert

AU - Holm, Louise Mannerås

AU - Tremaroli, Valentina

AU - Cani, Patrice D

AU - Bäckhed, Fredrik

N1 - Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

PY - 2017/11

Y1 - 2017/11

N2 - OBJECTIVE: Gut microbiota modulates adiposity and glucose metabolism in humans and mice. Here we investigated how colonization of germ-free (GF) mice affects kinetics of adiposity and glucose metabolism.METHODS: Adiposity and glucose metabolism were evaluated at different time points in ex-GF and antibiotic treated mice after colonization with gut microbiota from a conventionally raised (CONV-R) mouse. Mouse physiology, microbiome configuration, serum cytokine levels, and gene expression for inflammatory markers were performed in different tissues.RESULTS: Colonization resulted in a bi-phasic glucose impairment: the first phase occurring within 3 days of colonization (early phase) and the second 14-28 days after colonization (delayed phase). The early phase co-occurred with an inflammatory response and was independent of adiposity, while the delayed phase was mostly ascribed to adipose tissue expansion and inflammation. Importantly, re-colonization of antibiotic treated mice displays only the delayed phase of glucose impairment and adiposity, suggesting that the early phase may be unique to colonization of the immature GF mice gut.CONCLUSIONS: Our results provide new insights on host-microbiota interaction during colonization of GF mice and the resulting effects on adiposity and glucose metabolism in a time resolved fashion.

AB - OBJECTIVE: Gut microbiota modulates adiposity and glucose metabolism in humans and mice. Here we investigated how colonization of germ-free (GF) mice affects kinetics of adiposity and glucose metabolism.METHODS: Adiposity and glucose metabolism were evaluated at different time points in ex-GF and antibiotic treated mice after colonization with gut microbiota from a conventionally raised (CONV-R) mouse. Mouse physiology, microbiome configuration, serum cytokine levels, and gene expression for inflammatory markers were performed in different tissues.RESULTS: Colonization resulted in a bi-phasic glucose impairment: the first phase occurring within 3 days of colonization (early phase) and the second 14-28 days after colonization (delayed phase). The early phase co-occurred with an inflammatory response and was independent of adiposity, while the delayed phase was mostly ascribed to adipose tissue expansion and inflammation. Importantly, re-colonization of antibiotic treated mice displays only the delayed phase of glucose impairment and adiposity, suggesting that the early phase may be unique to colonization of the immature GF mice gut.CONCLUSIONS: Our results provide new insights on host-microbiota interaction during colonization of GF mice and the resulting effects on adiposity and glucose metabolism in a time resolved fashion.

KW - Journal Article

U2 - 10.1016/j.molmet.2017.08.016

DO - 10.1016/j.molmet.2017.08.016

M3 - Journal article

C2 - 29107285

SN - 2212-8778

VL - 6

SP - 1371

EP - 1380

JO - Molecular Metabolism

JF - Molecular Metabolism

IS - 11

ER -