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Nat Commun. 2018 Jul 20;9(1):2872. doi: 10.1038/s41467-018-05336-9.

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

Author information

1
Regulatory Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA, 92037, USA. azarrinp@ucsd.edu.
2
Division of Gastroenterology, University of California, San Diego, 9500 Gilman Drive, MC 0983, La Jolla, CA, 92093-0983, USA. azarrinp@ucsd.edu.
3
Center for Microbiome Innovation, University of California, San Diego, 9500 Gilman Drive, MC 0436, La Jolla, CA, 92093-0436, USA. azarrinp@ucsd.edu.
4
Division of Gastroenterology, VA San Diego Health Systems, 3350 La Jolla Village Drive, MC 9111D, La Jolla, CA, 92161, USA. azarrinp@ucsd.edu.
5
Regulatory Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
6
Center for Microbiome Innovation, University of California, San Diego, 9500 Gilman Drive, MC 0436, La Jolla, CA, 92093-0436, USA.
7
Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, MC 0763, La Jolla, CA, 92093-0763, USA.
8
Department of Computer Science and Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
9
Integrative Genomics and Bioinformatics Core, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
10
Division of Endocrinology, University of California, San Diego, 9500 Gilman Drive #0640, La Jolla, CA, 92093-0640, USA.
11
Protein Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
12
Regulatory Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA, 92037, USA. panda@salk.edu.

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.

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