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:	101/58 38 38/22 38/23 38/39 38/77 38/88 38/90 38/91 45 59 631/326/2565/2134 631/443/319/1557 631/443/319/320 64/60 96/98 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
Online Access:	Get full text
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Abstract	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.
AbstractList	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. 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 (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 (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 (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. 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.
ArticleNumber	2872
Author	Zarrinpar, Amir Panda, Satchidananda Chaix, Amandine Saghatelian, Alan Xu, Zhenjiang Z. Marotz, Clarisse A. Knight, Rob Chang, Max W.
Author_xml	– sequence: 1 givenname: Amir orcidid: 0000-0001-6423-5982 surname: Zarrinpar fullname: Zarrinpar, Amir email: azarrinp@ucsd.edu organization: Regulatory Biology Laboratory, The Salk Institute, Division of Gastroenterology, University of California, San Diego, Center for Microbiome Innovation, University of California, San Diego, Division of Gastroenterology, VA San Diego Health Systems – sequence: 2 givenname: Amandine orcidid: 0000-0001-7007-197X surname: Chaix fullname: Chaix, Amandine organization: Regulatory Biology Laboratory, The Salk Institute – sequence: 3 givenname: Zhenjiang Z. surname: Xu fullname: Xu, Zhenjiang Z. organization: Center for Microbiome Innovation, University of California, San Diego, Department of Pediatrics, University of California, San Diego, Department of Computer Science and Engineering, University of California, San Diego – sequence: 4 givenname: Max W. orcidid: 0000-0002-4526-489X surname: Chang fullname: Chang, Max W. organization: Integrative Genomics and Bioinformatics Core, The Salk Institute, Division of Endocrinology, University of California, San Diego – sequence: 5 givenname: Clarisse A. surname: Marotz fullname: Marotz, Clarisse A. organization: Center for Microbiome Innovation, University of California, San Diego, Department of Pediatrics, University of California, San Diego – sequence: 6 givenname: Alan surname: Saghatelian fullname: Saghatelian, Alan organization: Protein Biology Laboratory, The Salk Institute – sequence: 7 givenname: Rob surname: Knight fullname: Knight, Rob organization: Center for Microbiome Innovation, University of California, San Diego, Department of Pediatrics, University of California, San Diego, Department of Computer Science and Engineering, University of California, San Diego – sequence: 8 givenname: Satchidananda surname: Panda fullname: Panda, Satchidananda email: panda@salk.edu organization: Regulatory Biology Laboratory, The Salk Institute
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Snippet	Antibiotic-induced microbiome depletion (AIMD) has been used frequently to study the role of the gut microbiome in pathological conditions. However, unlike... Antibiotic-induced microbiome depletion is one of the most common approaches to modulate the gut microbiome. Here the authors demonstrate that it affects gut...
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Title	Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism
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