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

被引：378

作者：

Zarrinpar, Amir ^{[1
,2
,3
,4
]}

Chaix, Amandine ^{[1
]}

Xu, Zhenjiang Z. ^{[3
,5
,6
]}

Chang, Max W. ^{[7
,9
]}

Marotz, Clarisse A. ^{[3
,5
]}

Saghatelian, Alan ^{[8
]}

Knight, Rob ^{[3
,5
,6
]}

Panda, Satchidananda ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Regulatory Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Div Gastroenterol, 9500 Gilman Dr,MC 0983, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Ctr Microbiome Innovat, 9500 Gilman Dr,MC 0436, La Jolla, CA 92093 USA

[4] VA San Diego Hlth Syst, Div Gastroenterol, 3350 La Jolla Village Dr,MC 9111D, La Jolla, CA 92161 USA

[5] Univ Calif San Diego, Dept Pediat, 9500 Gilman Dr,MC 0763, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Dept Comp Sci & Engn, 9500 Gilman Dr, La Jolla, CA 92093 USA

[7] Salk Inst Biol Studies, Integrat Genom & Bioinformat Core, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[8] Salk Inst Biol Studies, Prot Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[9] Univ Calif San Diego, Div Endocrinol, 9500 Gilman Dr 0640, La Jolla, CA 92093 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

GLUCAGON-LIKE PEPTIDE-1; BILE-ACID METABOLISM; INTESTINAL MICROBIOTA; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; RESISTANCE; DIET; PROLIFERATION; MODULATION; VANCOMYCIN;

D O I：

10.1038/s41467-018-05336-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

共 51 条

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