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Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism.

Amir Zarrinpar | Amandine Chaix | Zhenjiang Z Xu | Max W Chang | Clarisse A Marotz | Alan Saghatelian | Rob Knight | Satchidananda Panda
Nature communications | 2018

Antibiotic-induced microbiome depletion (AIMD) has been used frequently to study the role of the gut microbiome in pathological conditions. However, unlike germ-free mice, the effects of AIMD on host metabolism remain incompletely understood. Here we show the effects of AIMD to elucidate its effects on gut homeostasis, luminal signaling, and metabolism. We demonstrate that AIMD, which decreases luminal Firmicutes and Bacteroidetes species, decreases baseline serum glucose levels, reduces glucose surge in a tolerance test, and improves insulin sensitivity without altering adiposity. These changes occur in the setting of decreased luminal short-chain fatty acids (SCFAs), especially butyrate, and the secondary bile acid pool, which affects whole-body bile acid metabolism. In mice, AIMD alters cecal gene expression and gut glucagon-like peptide 1 signaling. Extensive tissue remodeling and decreased availability of SCFAs shift colonocyte metabolism toward glucose utilization. We suggest that AIMD alters glucose homeostasis by potentially shifting colonocyte energy utilization from SCFAs to glucose.

Pubmed ID: 30030441

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK115214
  • Agency: NCATS NIH HHS, United States
    Id: KL2 TR000099
  • Agency: NIDDK NIH HHS, United States
    Id: R24 DK080506
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001442
  • Agency: NCATS NIH HHS, United States
    Id: TL1 TR001443
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007202
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK091618
  • Agency: NIDDK NIH HHS, United States
    Id: R03 DK114536
  • Agency: NEI NIH HHS, United States
    Id: P30 EY019005
  • Agency: NIGMS NIH HHS, United States
    Id: P50 GM085764
  • Agency: NIDDK NIH HHS, United States
    Id: U24 DK097153
  • Agency: NIDDK NIH HHS, United States
    Id: K08 DK102902
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014195

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