Project description:Abdominal surgeries are lifesaving procedures but can be complicated by the formation of peritoneal adhesions, intra-abdominal scars that cause intestinal obstruction, pain, infertility, and significant health costs. Despite this burden, the mechanisms underlying adhesion formation remain unclear and no cure exists. Here, we show that contamination of gut microbes increases post-surgical adhesion formation. Using genetic lineage tracing we show that adhesion myofibroblasts arose from the mesothelium. This transformation was driven by epidermal growth factor receptor (EGFR) signaling. The EGFR ligands Amphiregulin and Heparin-binding Epidermal Growth Factor, were sufficient to induce these changes. Correspondingly, EGFR inhibition led to a significant reduction of adhesion formation in mice. Adhesions isolated from human patients were enriched in EGFR positive cells of mesothelial origin and human mesothelium showed an increase of mesothelial EGFR expression during bacterial peritonitis. In conclusion, bacterial contamination drives adhesion formation through mesothelial EGFR signaling. This mechanism may represent a therapeutic target for the prevention of adhesions after intra-abdominal surgery.
Project description:Xiangjiang River (Hunan, China) has been contaminated with heavy metal for several decades by surrounding factories. However, little is known about the influence of a gradient of heavy metal contamination on the diversity, structure of microbial functional gene in sediment. To deeply understand the impact of heavy metal contamination on microbial community, a comprehensive functional gene array (GeoChip 5.0) has been used to study the functional genes structure, composition, diversity and metabolic potential of microbial community from three heavy metal polluted sites of Xiangjiang River. Three groups of samples, A, B and C. Every group has 3 replicates.
Project description:Xiangjiang River (Hunan, China) has been contaminated with heavy metal for several decades by surrounding factories. However, little is known about the influence of a gradient of heavy metal contamination on the diversity, structure of microbial functional gene in sediment. To deeply understand the impact of heavy metal contamination on microbial community, a comprehensive functional gene array (GeoChip 5.0) has been used to study the functional genes structure, composition, diversity and metabolic potential of microbial community from three heavy metal polluted sites of Xiangjiang River.
Project description:Pancreatic cancer is among the deadliest cancers that affects almost 54,000 patients in United States alone, with 90% of them succumbing to the disease. Lack of early detection is considered to be the foremost reason for such dismal survival rates. Our study shows that resident gut microbiota is altered at the early stages of tumorigenesis much before development of observable tumors in a spontaneous, genetically engineered mouse model for pancreatic cancer. In the current study, we analyzed the microbiome of in a genetic mouse model for PDAC (KRASG12DTP53R172HPdxCre or KPC) and age-matched controls using WGS at very early time points of tumorigenesis. During these time points, the KPC mice do not show any detectable tumors in their pancreas. Our results show that at these early time points, the histological changes in the pancreas correspond to a significant change in certain gut microbial population. Our predictive metabolomic analysis on the identified bacterial species reveal that the primary microbial metabolites involved in progression and development of PDAC tumors are involved in polyamine metabolism.
Project description:Background: The differential abundance of cell-free RNAs in bodily fluids is emerging as a promising tool for the non-invasive molecular diagnosis of cancer. Human saliva is considered a promising source of non-invasive biomarkers of diagnostic value for oral cancer detection. This study aims to identify diagnostic potent salivary RNAs in oral squamous cell carcinoma (OSCC)-patients by RNA-Sequencing. Method: Unstimulated saliva was collected from 5 normal control (NC) individuals and 9 OSCC patients (PS) with prior consent and ethical committee approvals. Total RNA isolated from cell-free saliva (CFS) supernatant was used to prepare small RNA libraries and sequenced on the Ion Torrent S5 platform. The sequencing reads were aligned to the human genome (hg19) using Bowtie 2, and the differential expression analysis was performed using RUVSeq and DESeq2. Mapped reads were screened across miRBase (v22) annotations for miRNAs and Gencode (v19) annotation for other RNAs. Reads were quantified by the Featurecount (v1.4.6) module of the R-package. The microbial-RNA enrichment analysis was determined using the One Codex platform. Result: RNA-sequencing detected protein-coding transcripts (PCTs), long-intergenic RNAs (lincRNAs), microRNAs (miRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs) and pseudogenes from the saliva of PS and HC samples. Transcriptome analyses revealed 89 PCTs, 18 lincRNAs and 6 miRNAs differentially expressed between PS and HC with a log2fold change ≥ 1 or ≤ -1 and p-value < 0.05. Gene ontology and pathway enrichment analyses indicated a significant correlation of the identified PCTs and miRNAs to various cancer-related pathways that may have implications in the pathogenesis of OSCC. Interestingly, unmapped non-human reads aligned to the microbial reference genomes. Further analyses of these microbial sequence reads revealed a significant microbial dysbiosis differentiating PS from HC. Metabolic pathways and functional analysis of the identified microbial phylotypes showed gene ontologies associated with inflammation, cell proliferation, ROS generation, and a range of metabolic processes. Conclusion: We report novel panels of differentially expressed PCTs, miRNAs and lincRNAs distinguishing PS from HC. Importantly, our results also provide evidence for oral microbial dysbiosis that appears to have pathological implications in OSCC. Summarily, this study provides a comprehensive landscape of salivary RNAs that can be exploited as non-invasive biomarkers for OSCC detection.
Project description:Oral microbial homeostasis is a key factor affecting oral health, and saliva plays a significant role in maintaining oral microbial homeostasis. The submandibular gland (SMG) and sublingual gland (SLG) together produce the most saliva at rest. Organic ingredients, including antimicrobial proteins, are rich and distinctive and depend on the type of acinar cells in the SMG and SLG. However, the functions of the SMG and SLG in maintaining oral microbial homeostasis have been difficult to identify and distinguish, given their unique anatomical structures. Therefore, we analyzed each gland using single-cell RNA sequencing.
2023-01-03 | GSE216476 | GEO
Project description:Microbial contamination of human samples
Project description:Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by co-culture with the oral pathogenic Porphyromonas gingivalis and Aggregatibacter (formerly actinobacillus) actinomycetemcomitans. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: Gingival epithelial HIGK cells were sham infected (CTRL) and infected with either the oral pathogenic P. gingivalis (Pg) or A. actinomycetemcomitans (Aa). These samples were hybridized to Affymetrix microarrays. Understanding how host cells have adapted to pathogens, and how barrier cells respond to limit their impact, provides a mechanistic biological basis of microbial disease in the mixed bacterial-human ecosystem of the oral cavity.
Project description:The response of soil microbial community to climate warming through both function shift and composition reorganization may profoundly influence global nutrient cycles, leading to potential significant carbon release from the terrain to the atmosphere. Despite the observed carbon flux change in northern permafrost, it remains unclear how soil microbial community contributes to this ecosystem alteration. Here, we applied microarray-based GeoChip 4.0 to investigate the functional and compositional response of subsurface (15~25cm) soil microbial community under about one year’s artificial heating (+2°C) in the Carbon in Permafrost Experimental Heating Research site on Alaska’s moist acidic tundra. Statistical analyses of GeoChip signal intensities showed significant microbial function shift in AK samples. Detrended correspondence analysis and dissimilarity tests (MRPP and ANOSIM) indicated significant functional structure difference between the warmed and the control communities. ANOVA revealed that 60% of the 70 detected individual genes in carbon, nitrogen, phosphorous and sulfur cyclings were substantially increased (p<0.05) by heating. 18 out of 33 detected carbon degradation genes were more abundant in warming samples in AK site, regardless of the discrepancy of labile or recalcitrant C, indicating a high temperature sensitivity of carbon degradation genes in rich carbon pool environment. These results demonstrated a rapid response of northern permafrost soil microbial community to warming. Considering the large carbon storage in northern permafrost region, microbial activity in this region may cause dramatic positive feedback to climate change, which is important and necessary to be integrated into climate change models.