Dataset Information

Integrated Metagenomics and Metabolomics to Reveal the Effects of Policosanol on Modulating the Gut Microbiota and Lipid Metabolism in Hyperlipidemic C57BL/6 Mice

ABSTRACT: The aim of the study was to investigate the regulatory effects of policosanol on hyperlipidemia, gut microbiota and metabolic status in a C57BL/6 mouse model. A total of 35 C57BL/6 mice were assigned to 3 groups, chow (n=12), high fat diet (HFD, n=12) and HFD+policosanol (n=11), then treated for 18 weeks. Policosanol supplementation significantly reduced serum triglycerides and total cholesterol, as well as the weight of brown adipose tissue (BAT) (p<0.05), without affecting body weight in HFD-fed mice (p>0.05). Combined 16S rRNA gene sequencing and untargeted metabolomic analysis demonstrated that policosanol had regulatory effects on gut microbiota and serum metabolism in mice. In obese mice, policosanol increased the proportion of Bacteroides, decreased the proportion of Firmicutes, and increased the ratio of Bacteroides to Firmicutes (p<0.05). Policosanol promoted lipolysis and thermogenesis process, including tricarboxylic acid (TCA) cycle and pyruvate cycle, correlated with the increasing level of Bacteroides, Parasutterella, and decreasing level of Lactobacillus and Candidatus_Saccharimonas. Moreover, policosanol decreased fatty acid synthase (FAS) in the iWAT of obese mice. Policosanol also increased peroxisome proliferators-activated receptor-γ (PPARγ), uncoupling Protein-1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PR domain containing 16 (PRDM16) in brown adipose tissue (BAT) obese mice (p<0.05). This study presents the new insight that policosanol may inhibit the synthesis of fatty acids, and promote lipolysis, thermogenesis related gene expression and regulate gut microbiota constituents, which provides potential for policosanol as an antihyperlipidemia functional food additive and provide new evidence for whole grain food to replace refined food.

SUBMITTER: Zhai Z

PROVIDER: S-EPMC8542985 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The present study is undertaken to assess the alleviating effects of antimicrobial peptide cecropin A on inflammatory bowel disease (IBD) in C57BL/6 mice and changes in the gut microbiota, compared to an antibiotic gentamicin. Different doses of cecropin A were intraperitoneally injected into C57BL/6 mice for 5 days to determine the safe doses. The injection doses at ≤ 15 mg/kg showed no negative impact on the liver, heart, spleen, and kidney. The severe and moderate IBD mice model was successfully established via supplementation of 4 or 2.5% dextran sulfate sodium (DSS) in drinking water for 5 days. The severe IBD model was used to ensure the optimal therapeutic dose of cecropin A. Survival rate, body weight and disease activity index (DAI) scores were measured. Administration of 15 mg/kg, not 5 mg/kg cecropin A, for 5 days increased survival rate and decreased body weight loss of mice. The moderate IBD model was applied to investigate the mechanisms for cecropin A to alleviate inflammation in comparison to gentamicin. The mice were treated with 15 mg/kg cecropin A or 5 mg/kg gentamicin for 3 days. The levels of cytokines and related proteins in the colon were detected by ELISA and Western blotting. The microbiota in cecum contents were analyzed using 16S rRNA gene sequencing. The results showed that cecropin A and gentamicin relieved body weight loss, DAI, and gut mucosa disruption, while decreasing tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), and interlukin-6 (IL-6) induced by DSS. In addition, cecropin A and gentamicin showed different effects on the gut microbiota structure. Both cecropin A and gentamicin decreased DSS-induced enrichment of Bacteroidaceae and Enterobacteriaceae. However, cecropin A showed a selective enrichment of Lactobacillus in contrast to gentamicin, which demonstrated a selective effect on Desulfovibrionaceae and Ruminococcaceae. Cecropin A alleviates IBD through decreasing harmful gut microflora and specifically enhancing beneficial gut microflora. The mechanism of this effect is different from gentamicin.

Project description:The human intestine is host to an enormously complex, diverse, and vast microbial community-the gut microbiota. The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development, epithelial homeostasis, and so forth. However, the composition and diversity of the gut microbiome can be readily affected by external factors, which raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration, or dysbiosis. Arsenic exposure affects large human populations worldwide and has been linked to a number of diseases, including cancer, diabetes, and cardiovascular disorders.We investigated the impact of arsenic exposure on the gut microbiome composition and its metabolic profiles.We used an integrated approach combining 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling to examine the functional impact of arsenic exposure on the gut microbiome.16S rRNA gene sequencing revealed that arsenic significantly perturbed the gut microbiome composition in C57BL/6 mice after exposure to 10 ppm arsenic for 4 weeks in drinking water. Moreover, metabolomics profiling revealed a concurrent effect, with a number of gut microflora-related metabolites being perturbed in multiple biological matrices.Arsenic exposure not only alters the gut microbiome community at the abundance level but also substantially disturbs its metabolic profiles at the function level. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism by which arsenic exposure leads to or exacerbates human diseases.Lu K, Abo RP, Schlieper KA, Graffam ME, Levine S, Wishnok JS, Swenberg JA, Tannenbaum SR, Fox JG. 2014. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis. Environ Health Perspect 122:284-291;?http://dx.doi.org/10.1289/ehp.1307429.

Project description:Hepatectomy is a common clinical procedure for the treatment of many liver diseases, and the successful recovery of a patient's liver metabolism and function after surgery is crucial for a good prognosis. The objective of this study was to elucidate the metabolic response to hepatectomy using high-throughput sequencing analysis of 16S rRNA gene, metabolomics, and proteomics data. Fecal and serum samples from beagle dogs were collected on day 0 (LH0), day 7 (LH7), and day 28 (LH28) after laparoscopic partial hepatectomy. Liver tissue samples were taken on LH0 and LH7. Dysbiosis in the fecal microbiota was explored, and host-microbiome interactions based on global metabolic and protein profiles and inflammatory processes were determined. Results showed that the relative abundance of Allobaculum and Turicibacter was decreased and that of Escherichia-Shigella was increased after hepatectomy (P < 0.05); the phenylalanine, tyrosine, and tryptophan biosynthetic pathway, along with the phenylalanine and aminoacyl-tRNA biosynthetic pathway, was significantly associated with liver injury. The serum metabolites l-phenylalanine and l-arginine were useful as biomarkers, and the fecal metabolite l-threonine was a signature target monitor for liver recovery. The proteomics profile revealed 412 significantly different proteins and further highlighted two key signaling pathways (mitogen-activated protein kinase [MAPK] and peroxisome proliferator-activated receptor [PPAR]) involved in the response to liver injury. We systematically explored the metabolic mechanism of liver injury and recovery, providing new insights into effective ways to promote recovery after hepatectomy and improve liver function and long-term survival. These fundamental studies on hepatectomy will provide the basis for future advances in treatment and recovery from common liver diseases. IMPORTANCE As the largest parenchymal organ, the liver is a target for bacterial and viral infections, nonalcoholic fatty liver disease (NAFLD), cirrhosis, cancer, and many other diseases, constituting a serious worldwide problem. The treatment for many of these diseases involves hepatectomy. Here, we show that aberrant inflammatory processes after hepatectomy of the liver as reflected in the association between liver metabolism and gut microbiota create a grave risk. This study investigated the mechanisms of gut microbiota and host metabolism involved in liver injury and recovery after hepatectomy, using proteomics to reveal the mechanisms of postoperative liver injury and a comprehensive multi-omics approach to identify changes in metabolism after hepatectomy.

Dataset Information

Integrated Metagenomics and Metabolomics to Reveal the Effects of Policosanol on Modulating the Gut Microbiota and Lipid Metabolism in Hyperlipidemic C57BL/6 Mice

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets