Project description:Background: Prevention of hyperlipidemia and associated diseases is a health priority. Complementary medicine based on scientific evidence has recently recognized the potential of natural products for modulating lipid metabolism, such as the medicinal mushroom Ganoderma lucidum (Gl), which possesses hypocholesterolemic, prebiotic and antidiabetic properties. Methods: Whole-transcriptomic changes in liver and kidney from a mouse model (C57BL/6), under a high-cholesterol diet and standardized Gl extracts (Gl-1, Gl-2) or simvastatin administration, were analyzed to determine Gl hypocholesterolemic activity. Further effects of Gl extracts on lipid metabolism were evaluated using an in vitro hepatic-like macrophage model. Additionally, correlations among hepatic gene expression, microbiota and serum lipid profiles in vivo established by Gl extracts were evaluated. Results: Based on the hepatic and renal mRNA profiles of mice treated with Gl extracts and high-cholesterol diet, we identified relevant metabolic pathways modulated by Gl involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. We further showed that Gl extracts induce a significant decrease of macrophage lipid storage and cholesterol biosynthesis, which occurs concomitantly by the down-modulation of Fasn and Elovl6. We also determined that prebiotic effects of Gl extracts modulating gut microbiota are correlated with the gene expression portraits. Conclusions: Our high-throughput analysis allowed to identify key transcriptomic nodes established by Gl extracts and their interaction with microbiome composition related to lipid catabolic signaling. Our results indicated that our Gl extracts have a robust potential to be used as transcriptome modulators and prebiotic agents to prevent metabolic disorders associated to hypercholesterolemia.
Project description:Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD) with complex etiology involving chronic inflammation, immune dysregulation, and gut microbiota dysbiosis. Creatine, a natural nitrogenous com-pound, possesses anti-inflammatory and immunomodulatory properties, but its role in CAC remains unclear.We established an AOM/DSS-induced mouse model of CAC and supplemented mice with creatine. We assessed the effects of creatine on colitis severity, tumor burden, and histopathology. Additionally, we investigated the impact of crea-tine on gut barrier function, macrophage polarization, and gut microbiota composi-tion.Creatine supplementation significantly alleviated DSS-induced colitis, reduced tumor burden, and delayed CAC progression in mice. Mechanistically, creatine im-proved gut barrier function by protecting tight junction proteins from degradation in-duced by the modeling stimulus,influenced macrophage polarization, and main-tained gut microbiota diversity, promoting the abundance of beneficial bacteria while reducing harmful ones.Our findings suggest that creatine supplementation may rep-resent a promising supportive therapy for IBD and CAC by modulating the gut micro-biota and immune microenvironment. Further investigation is warranted to explore the clinical potential of creatine in the management of CAC.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver Wild-type C57Bl/6 male mice 11 weeks of age were fed isocaloric diets (45% kcal fat) with either menhaden fish oil (Research Diets, D05122102) or lard (Research Diets, D10011202) for 11 weeks. Liver samples were harvested at the end of the experiment and analyzed by microarray.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in epididymal adipiose tissue (EWAT) Wild-type C57Bl/6 male mice 11 weeks of age were fed isocaloric diets (45% kcal fat) with either menhaden fish oil (Research Diets, D05122102) or lard (Research Diets, D10011202) for 11 weeks. Epididymal WAT samples were harvested at the end of the experiment and analyzed by microarray.
Project description:Gut microbiota plays an important role during early development via bidirectional gut- brain signaling. We aimed to explore the potential link between gut microbiota/gut derived metabolites and sympathoadrenal stress responsivity
Project description:Intracerebral hemorrhage (ICH) induces alterations in the gut microbiota composition, significantly impacting neuroinflammation post-ICH. However, the impact of gut microbiota absence on neuroinflammation following ICH-induced brain injury remain unexplored. Here, we observed that the gut microbiota absence was associated with reduced neuroinflammation, alleviated neurological dysfunction, and mitigated gut barrier dysfunction post-ICH. In contrast, recolonization of microbiota from ICH-induced SPF mice by transplantation of fecal microbiota (FMT) exacerbated brain injury and gut impairment post-ICH. Additionally, microglia with transcriptional changes mediated the protective effects of gut microbiota absence on brain injury, with Apoe emerging as a hub gene. Subsequently, Apoe deficiency in peri-hematomal microglia was associated with improved brain injury. Finally, we revealed that gut microbiota influence brain injury and gut impairment via gut-derived short-chain fatty acids (SCFA).
Project description:Microbiota from rats fed with wheat aleurone and plant omega fatty acids In this study we investigated how an AX-rich WA and ALA from linseed oil (LO) modulate the gut microbiota of rats. Wistar rats were fed a standard diet and received either an iso-energetic control oil (PO), control oil + aleurone (A+PO), linseed oil (LO) or linseed oil + aleurone (A+LO) during 12 weeks. Feacal samples were recovered after the 12 week treatments. DNA extractions were performed using using the Qiagen's DNA Stool Kit (Qiagen, West Sussex, UK). 10ng of DNA template were amplified by PCR (16S gene) and purified using Qiagen's Qiaquick PCR purification kit (Qiagen, West Sussex, UK). 1ug of purified PCR product were labelled with either Cy3 or Cy5 using Genomic DNA ULS Labelling kit (Agilent Technologies, Palo Alto, CA). 250ng of labelled DNA were hybridized on the microarray for 24h at 65M-BM-0C. Washings were performed as recommended by the manufacturer. Microarray scanning was performed on a Surescan Microarray scanner (Agilent Technologies, Palo Alto, CA). Data were extracted using the Feature extraction software (Agilent Technologies, Palo Alto, CA). The retained intensity value for each probe was the ratio between the spotM-bM-^@M-^Ys median intensity signals and the median of background signals. A 13 chip study was realized to analyze the feacal microbiota of rats treated with either an iso-energetic control oil (PO), control oil + aleurone (A+PO), linseed oil (LO) or linseed oil + aleurone (A+LO) during 12 weeks. Each microarray corresponding to hybridization with 250ng of labelled 16S rRNA gene amplicons from 2 rat DNA faecal samples. Microbiota structure and diversity were assessed using the HuGChip (Tottey et al., 2013). Each probe (4441) was synthetized in three replicates. On the same array, 2 different samples were hybridized. One labelled with the Cy3 dye and one with the Cy5 dye. The results were processed as single channel (13 raw data files available on Series records for 25 samples).