Project description:Localization of Fusobacterium nucleatum in the placenta may be associated with pregnancy complications including preeclampsia (PE), but its specific pathobiology is unknown. Our aim was to analyze the effect of Fusobacterium nucleatum on HUVEC cells to further elucidate placental dysfunction in the context of Fusobacterium nucleatum infestation.
Project description:Fusobacterium nucleatum-treated LoVo cells reported an increased promoting CRC metastasis effect compared with PBS control. To understand the underlying mechanisms of Fusobacterium nucleatum-induced metastasis ability of CRC cells, we performed RNA-sequencing in LoVo cells s with or without Fusobacterium nucleatum treatment with three independent biological replicates.
Project description:Fusobacterium nucleatum-treated HCT116 cells reported an increased adhesion to endothelial cells compared with PBS control. To understand the underlying mechanisms of Fusobacterium nucleatum-induced intercellular adhesion ability of CRC cells, we performed RNA-sequencing in HCT116 cells with or without Fusobacterium nucleatum treatment with three independent biological replicates.
Project description:To investigate the role of Fusobacterium nucleatum-mediated m6A modification, we performed m6A-sequencing to map the m6A modification in control or Fusobacterium nucleatum-treated HCT116 cells.
Project description:To investigate the effect of the Zn ionophore, PBT2, on the transcriptomic response of Fusobacterium nucleatum ATCC 25586, RNA was extracted from bacterial samples which had been treated as follows: Untreated (0.006% DMSO v/v), DMSO-Zn treated (0.006% DMSO v/v + 200 uM ZnSO4), or PBT2-Zn treated (0.125 ug/mL PBT2 + 200 uM ZnSO4) (DMSO was the vehicle control). RNA samples were collected at 0h, 0.5h, and 1h post challenge in biological triplicate and sequenced using Illumina HiSeq platform. We mapped sequences to the reference genome F. nucleatum subsp. nucleatum ATCC 25586 and performed DEseq2 analysis to determine differentially expressed genes across time and treatment.
Project description:Fusobacterium nucleatum is a Gram-negative oncobacterium that is associated with colorectal cancer. The molecular mechanisms utilized by F. nucleatum to promote colorectal tumor development have largely focused on adhesin-mediated binding to the tumor tissue and on the pro-inflammatory capacity of F. nucleatum. However, the exact manner in which F. nucleatum promotes inflammation in the tumor microenvironment and subsequent tumor promotion remains underexplored. Here, we show that both live F. nucleatum and sterile F. nucleatum-conditioned medium promote CXCL8 release from the intestinal adenocarcinoma HT-29 cell line. We determined that the pro-inflammatory response was ALPK1-dependent in both HEK293 and HT-29 cells and that the released F. nucleatum molecule had characteristics that match those of the pro-inflammatory ALPK1 ligand ADP-heptose or related heptose phosphates. In addition, not only F. nucleatum but also other Fusobacterium species such as F. varium, F. necrophorum and F. gonidiaformans promoted an ALPK1-dependent pro-inflammatory environment, indicating that ADP-heptose or related heptose phosphates secretion is a conserved feature of the Fusobacterium genus. By performing transcriptional analysis of ADP-heptose stimulated HT-29 cells, we found several inflammatory and cancer-related pathways to be differentially regulated, including DNA mismatch repair genes and the immune inhibitory receptor PD-L1. Finally, we show that stimulation of HT-29 cells with F. nucleatum resulted in an ALPK1-dependent upregulation of PD-L1. These results aid in our understanding of the mechanisms by which F. nucleatum can affect tumor development and therapy and pave the way for future therapeutic approaches.
Project description:Placental Fusobacterium nucleatum localization may be associated with pregnancy complications, including preeclampsia (PE), but nothing is known about its specific pathobiology. We aimed to perform transcriptomic analysis of the placentas of mice that were orally gavaged with Fusobacterium nucleatum or saline during pregnancy to further elucidate placental dysfunction in these conditions.
Project description:Fusobacterium nucleatum (F. nucleatum) contributes to the development of colorectal cancer (CRC) by inducing chronic inflammation. We found that iron deposition in macrophages is associated with poor prognosis of CRC patients with high amount of F. nucleatum. To explore the impact of iron on macrophage properties in the presence of F. nucleatum, we conducted RNA sequencing of THP-1 macrophages pretreated with ferric anmonium citrate (FAC) or deferoxamine (DFO), followed by treatment with F. nucleatum. Several chemokine genes were differentially increased in FAC-treated cells when compared with DFO-treated cells, suggesting that iron is required for the efficient induction of tumor-promoting chemokines in macrophages upon F. nucleatum infection. Our results suggest a prognostic role for iron in F. nucleatum-positive CRC.
Project description:Gut microbiome research is rapidly moving towards the functional characterization of the microbiota by means of shotgun meta-omics. Here, we selected a cohort of healthy subjects from an indigenous and monitored Sardinian population to analyze their gut microbiota using both shotgun metagenomics and shotgun metaproteomics. We found a considerable divergence between genetic potential and functional activity of the human healthy gut microbiota, in spite of a quite comparable taxonomic structure revealed by the two approaches. Investigation of inter-individual variability of taxonomic features revealed Bacteroides and Akkermansia as remarkably conserved and variable in abundance within the population, respectively. Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the functional activity with the higher expression rate and the lower inter-individual variability in the study cohort, highlighting the key importance of the biosynthesis of this microbial by-product for the gut homeostasis. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several gut microbiota members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis and short-chain fatty acid production). In conclusion, our results provide useful indications regarding the main functions actively exerted by the gut microbiota members of a healthy human cohort, and support metaproteomics as a valuable approach to investigate the functional role of the gut microbiota in health and disease.
Project description:Neutrophils are known to be stimulated by different periodontal bacteria to produce reactive oxygen species and cytokines. It is inportant to investigate the gene changes made by bacteria of importance, of which, for periodontal disease, fusobaterium nucleatum is one. we used microarrays to investigate gene experssion changes in peripheral blood neutrophils werwhich e stimulated with or with out Fusobacterium Nucleatum (10953). Neutrophils from periodonatlly healthy individuals (n=4) were isolated and stimulated for 3hrs with or without fusobaterium nucleatum (10953). RNA was then extracted from these and pooled before hybridization on Affymetrix microarrays