The Short-Day Cycle Induces Intestinal Epithelial Purine Metabolism Imbalance and Hepatic Disfunctions in Antibiotic-Mediated Gut Microbiota Perturbation Mice

Abstract

Intestinal microbiota dysbiosis is related to many metabolic diseases in human health. Meanwhile, as an irregular environmental light–dark (LD) cycle, short day (SD) may induce host circadian rhythm disturbances and worsen the risks of gut dysbiosis. Herein, we investigated how LD cycles regulate intestinal metabolism upon the destruction of gut microbes with antibiotic treatments. The growth indices, serum parameters, concentrations of short-chain fatty acids (SCFAs), and relative abundance of intestinal microbes were measured after euthanasia; intestinal contents, epithelial metabolomics, and hepatic transcriptome sequencing were also assessed. Compared with a normal LD cycle (NLD), SD increased the body weight, spleen weight, and serum concentration of aspartate aminotransferase, while it decreased high-density lipoprotein. Meanwhile, SD increased the relative abundance of the Bacteroidetes phylum while it decreased the Firmicutes phylum in the gut of ABX mice, thus leading to a disorder of SCFA metabolism. Metabolomics data revealed that SD exposure altered gut microbial metabolism in ABX mice, which also displayed more serious alterations in the gut epithelium. In addition, most differentially expressed metabolites were decreased, especially the purine metabolism pathway in epithelial tissue. This response was mainly due to the down-regulation of adenine, inosine, deoxyguanosine, adenylsuccinic acid, hypoxanthine, GDP, IMP, GMP, and AMP. Finally, the transcriptome data also indicated that SD has some negative effects on hepatic metabolism and endocrine, digestive, and disease processes. Overall, SD induced an epithelial and hepatic purine metabolism pathway imbalance in ABX mice, as well as the gut microbes and their metabolites, all of which could contribute to host metabolism and digestion, endocrine system disorders, and may even cause diseases in the host.

Multi-Omics Reveals the Impact of Exogenous Short-Chain Fatty Acid Infusion on Rumen Homeostasis: Insights into Crosstalk between the Microbiome and the Epithelium in a Goat Model

“…Briefly, 100 mg of rumen contents and epithelial tissue samples were first treated with 600 μL of methanol solution. Sample preparation was carried out as we described previously ( 65 ). LC-MS untargeted metabolome analysis was performed using a Vanquish UHPLC system (Thermo Fisher Scientific, Santa Clara, CA) with an Acquity UPLC HSS T3 column (150 mm × 2.1 mm, 1.8 μm; Waters, Milford, MA) at a column temperature of 40°C, a flow rate of 0.25 mL/min, and an injection volume of 2 μL at Panomix Biomedical Tech Co., Ltd. (Suzhou, Jiangsu, China).…”

Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light–dark cycles: A multiomics study

“…Data analysis steps for RNA‐Seq followed a previous study 38 . Briefly, the Fastp software (v0.23.1) 39 was first used to perform quality control (QC) on the raw data and obtain clean data.…”

“…Data analysis steps for RNA-Seq followed a previous study. 38 Briefly, the Fastp software (v0.23.1) 39 was first used to perform quality control (QC) on the raw data and obtain clean data. Then, the HISAT2 software (v2.1.0) 40 was used to align the obtained clean data referred to the latest reference genome in mouse (GRCm39).…”