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

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...

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Published in:Nature communications Vol. 9; no. 1; pp. 2872 - 13
Main Authors: Zarrinpar, Amir, Chaix, Amandine, Xu, Zhenjiang Z., Chang, Max W., Marotz, Clarisse A., Saghatelian, Alan, Knight, Rob, Panda, Satchidananda
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 20.07.2018
Nature Publishing Group
Nature Portfolio
Subjects:
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Adipose tissue
Amphotericin B - administration & dosage
Ampicillin - administration & dosage
Animals
Anti-Bacterial Agents - pharmacology
Antibiotics
Bile
Bile Acids and Salts - chemistry
Blood Glucose - metabolism
Body Composition
Body Weight
Cecum
Cecum - metabolism
Colon - drug effects
Colon - metabolism
Colon - microbiology
Depletion
Energy utilization
Fatty acids
Fatty Acids, Volatile - chemistry
Gastrointestinal Microbiome - drug effects
Gene expression
Gene Expression Regulation
Germfree
Glucagon
Glucagon-like peptide 1
Glucose
Glucose - metabolism
Glucose tolerance
Homeostasis
Humanities and Social Sciences
Insulin
Insulin - metabolism
Insulin Resistance
Intestinal microflora
Male
Metabolism
Metronidazole - administration & dosage
Mice
Mice, Inbred C57BL
Microbiomes
multidisciplinary
Neomycin - administration & dosage
Obesity - drug therapy
Obesity - metabolism
Obesity - microbiology
RNA, Ribosomal, 16S - metabolism
Science
Science (multidisciplinary)
Signaling
Vancomycin - administration & dosage
ISSN:2041-1723, 2041-1723
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Summary: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. Antibiotic-induced microbiome depletion is one of the most common approaches to modulate the gut microbiome. Here the authors demonstrate that it affects gut homeostasis and glucose metabolism by decreasing luminal short chain fatty acids and leading to a shift of energy utilization by colonocytes.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-05336-9