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Cecal transcriptome by Next Generation Sequencing of WT C57Bl/6 mice treated with water (vehicle) or with antibiotics (AIMD) to induce microbiome depletion .

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 is unknown. We investigated the effects of AIMD in normal-chow fed mice to understand its effects on gut homeostasis, luminal signaling, and metabolism. We show 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 occur in the setting of decreased luminal short-chain fatty acids (SCFAs), especially butyrate, and secondary bile acid (BA) pool, which affects whole-body BA metabolism. In mice, AIMD alters cecal gene expression and gut GLP-1 signaling. Extensive tissue remodeling and decreased availability of SCFAs shift colonocyte metabolism toward glucose utilization. Hence, AIMD alters whole-body glucose homeostasis by potentially shifting colonocyte energy utilization from SCFAs to glucose.

ORGANISM(S): Mus musculus

PROVIDER: GSE114818 | GEO | 2018/07/07

REPOSITORIES: GEO

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Project description:The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia, reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.

Dataset Information

Cecal transcriptome by Next Generation Sequencing of WT C57Bl/6 mice treated with water (vehicle) or with antibiotics (AIMD) to induce microbiome depletion .

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