Project description:The intestinal microbiota fundamentally influences the development of a normal intestinal physiology and education and functioning of the mucosal immune system. The goal of this study is to analyze how the transcriptional profile of the murine colon can be influence by colonization of gnotobiotic mice with specific bacterial strains .
Project description:The intestinal microbiota influences the development of a normal intestinal physiology, education and functioning of the mucosal immune system. The goal of this study is to analyze how the transcriptional profile of the colonic endothelial cells is influence by colonization of gnotobiotic mice with specific bacterial strains . The goal of this study is to analyze how the transcriptional profile of the colonic endothelial cells is influence by colonization of gnotobiotic mice with specific bacterial strains .
Project description:Laryngeal squamous cell carcinoma is a very common in head and neck cancer, accounting for 25% of all cases, with high mortality rates and poor prognosis. In this study, we compared expression profiles of clinical samples from15 larynx tumors and 10 non-neoplastic larynx tissue using a custom-built cDNA microarray containing 332 probes for 285 genes previously identified as up- or down-regulated in head and neck tumors by the Head and Neck Annotation Consortium (Reis et al., Cancer Res 65:1693-99, 2005). Thirty-five genes showed statistically significant differences (SNR ≥|1.0|,p-value ≤ 0.001) in expression between tumor and non-tumor larynx tissue samples. Functional annotation indicated that these genes are involved in cellular processes relevant to the cancer phenotype, such as apoptosis, cell cycle, DNA repair, proteolysis, protease inhibition, signal transduction, and transcription regulation. Six of the identified transcripts map to intronic regions of protein-coding genes and may comprise unannotated exons or yet uncharacterized long ncRNAs with a regulatory role in the gene expression program of larynx tissue. Differential expression of 10 of these genes (ADCY6, AES, AL2SCR3, CRR9, CSTB, DUSP1, MAP3K5, PLAT, UBL1 and ZNF706) was independently confirmed by quantitative real-time RT-PCR. Among these, the CSTB gene product has cysteine protease inhibitor activity that has been associated to an antimetastatic function. Interestingly, CSTB showed low expression in all tumor samples analyzed (p-value < 0.0001). The set of genes identified here contribute to a better understanding of the molecular basis of larynx cancer, and at the same time provide novel candidate markers for improving diagnosis, prognosis and treatment of this carcinoma. Keywords: Gene expression profiling of larynx tumors and non-neoplastic adjacent tissue
Project description:Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition.
Project description:Here, we report analysis of both the bacterial and host transcriptome as affected by colonization of R. hominis in the mouse gut. Microbial genes required for colonization and adaptation in the murine gut, as well as host genes responding to colonization by this bacterial species, were uncovered.
Project description:We discovered that colonization of the gut with the human bile acid 7'-dehydroxylating bacteria Clostridia scindens provided immunity to the parasite E. histolytica in a murine model, increased granulocyte monocyte progenitors, and that adoptive marrow transplant from C. scindens colonized mice into naive mice could recapitualte this protection.
Project description:Cigarette smoking is a major risk factor for laryngeal diseases. Despite well-documented cigarette smoke (CS) induced laryngeal histopathological changes in animal models and humans, the underlying immunopathological mechanisms remain largely unexplored. The goal of this study was to evaluate inflammatory and immune cell responses in a CS-exposed larynx. Specifically, we investigated these responses in the mouse larynx after a 4-week subacute low (LD) and high-dose (HD) whole-body mainstream CS exposure.
Project description:Cancer of the larynx is the second most common upper-aerodigestive cancer, and laryngeal squamous cell carcinoma (LSCC) is the major histological form. However, the molecular mechanism within LSCC progression remains poorly understood. MicroRNA-based target therapy is a promising approach in cancer therapy and offers multiple advantages as compared with the conventional treatment modalities. Hence, there is a need to identify the key microRNA involved in the progression of LSCC. We used GeneChip miRNA 2.0 array to profile the global microRNA deregulation in LSCC.
Project description:Understanding how the human gut microbiota and host are impacted by probiotic bacterial strains requires carefully controlled studies in humans, and in mouse models of the gut ecosystem where potentially confounding variables that are difficult to control in humans can be constrained. Therefore, we characterized the fecal microbiomes and metatranscriptomes of adult female monozygotic twin pairs through repeated sampling 4 weeks prior to, 7 weeks during, and 4 weeks following consumption of a commercially-available fermented milk product (FMP) containing a consortium of Bifidobacterium animalis subsp. lactis, two strains of Lactobacillus delbrueckii subsp. bulgaricus, Lactococcus lactis subsp. cremoris, and Streptococcus thermophilus. In addition, gnotobiotic mice harboring a 15-species model human gut microbiota whose genomes contain 58,399 known or predicted protein-coding genes were studied prior to and after gavage with all five sequenced FMP strains. 140 samples total. Evaluation of changes in a model community's structure over time after exposure to a consortium of 5 fermented milk product (FMP) strains.
Project description:We illustrate an approach for integrating preclinical gnotobiotic animal models with human studies to understand the contributions of perturbed gut microbiota development to childhood undernutrition, and to identify new microbiota-directed therapeutic concepts/leads. Combining metabolomic and proteomic analyses of serially collected plasma samples with metagenomic analyses of serially collected fecal samples, we characterized the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned to moderate acute malnutrition (MAM) after standard treatment. Gnotobiotic mice were subsequently colonized with a defined consortium of bacterial strains representing different stages of microbiota development in healthy children from Bangladesh. Administering different combinations of Bangladeshi complementary food ingredients to colonized mice and germ-free controls revealed diet-dependent changes in representation and metabolism of targeted weaning-phase strains, including accompanying increases in branched-chain amino acids, plus diet- and colonization-dependent augmentation of IGF-1/mTOR signaling. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes were subsequently examined in gnotobiotic mice colonized with post-SAM MAM microbiota and in gnotobiotic piglets colonized with a defined consortium of targeted age- and growth-discriminatory bacteria. Finally, ar andomized, double-blind study revealed a lead MDCF that affected the representation of targeted bacterial taxa and increased levels of biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function.