Project description:In this study, we performed a comparative analysis of gut microbiota composition and gut microbiome-derived bacterial extracellular vesicles (bEVs) isolated from patients with solid tumours and healthy controls. After isolating bEVs from the faeces of solid tumour patients and healthy controls, we performed spectrometry analysis of their proteomes and next-generation sequencing (NGS) of the 16S gene. We also investigated the gut microbiomes of faeces from patientsand controls using 16S rRNA sequencing. Machine learning was used to classify the samples into patients and controls based on their bEVs and faecal microbiomes.
Project description:The gut microbiome plays an important role in normal immune function and has been implicated in several autoimmune disorders. Here we use high-throughput 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=61) and healthy controls (n=43). Alterations in the gut microbiome in MS include increases in the genera Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signaling and NF-kB signaling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of the genera Prevotella and Sutterella, and decreased Sarcina, compared to untreated patients. MS patients of a second cohort show elevated breath methane compared to controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.
Project description:We randomly selected 60 patients who completed paclitaxel treatment for high-throughput sequencing. Grade 2 or higher (grade 2+) neuropathy has been defined as high-PIPN and Grade 1 as low-PIPN according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE version 4.0) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). We compared gut microbiome signatures in high-PIPN, low-PIPN, and healthy controls.
Project description:Hidradenitis suppurativa (HS) is an inflammatory skin disease with limited therapeutic options. Identifying transcriptional alterations within non-immune populations of HS lesions versus healthy controls could identify novel targets for therapy. We profiled subsets sorted as live, CD45 negative cells from biopsies of inflammatory lesions of three patients with HS and six specimens from healthy controls to determine what cell types and pathways were altered in HS inflammatory lesions.
Project description:To characterize proteomic signatures of platelet-derived medium-size EVs(mEVs) EVs of Colorectal cancer patients vs. healthy subjects (HS) matched for sex and age
2023-03-11 | PXD038674 | Pride
Project description:Gut microbiome analysis between IgAN patients and healthy controls
Project description:Rationale: Recent studies suggest a potential link between gut bacterial microbiota dysbiosis and PAH, but the exact role of gut microbial communities, including bacteria, archaea, and fungi, in PAH remains unclear. Objectives: To investigate the role of gut microbiota dysbiosis in idiopathic pulmonary arterial hypertension (IPAH) and to assess the therapeutic potential of fecal microbiota transplantation (FMT) in modulating PAH progression. Methods: Using shotgun metagenomics, we analyzed gut microbial communities in IPAH patients and healthy controls. FMT was performed to transfer gut microbiota from IPAH patients or MCT-PAH rats to normal rats and from healthy rats to MCT-PAH rats. Hemodynamic measurements, echocardiography, histological examination, metabolomic and RNA-seq analysis were conducted to evaluate the effects of FMT on PAH phenotypes. Measurements and Main Results: Gut microbiota analysis revealed significant alterations in the bacterial, archaeal, and fungal communities in IPAH patients compared to healthy controls. FMT from IPAH patients induced PAH phenotypes in recipient rats. Conversely, FMT from healthy rats to IPAH rats significantly ameliorated PAH symptoms, restored gut microbiota composition, and normalized serum metabolite profiles. Specific microbial species were identified with high diagnostic potential for IPAH, improving predictive performance beyond individual or combined microbial communities. Conclusions: This study establishes a causal link between gut microbiota dysbiosis and IPAH and demonstrates the therapeutic potential of FMT in reversing PAH phenotypes. The findings highlight the critical role of bacterial, archaeal, and fungal communities in PAH pathogenesis and suggest that modulation of the gut microbiome could be a promising treatment strategy for PAH.
Project description:Significant gut microbiota heterogeneity exists amongst UC patients though the clinical implications of this variance are unknown. European and South Asian UC patients exhibit distinct disease risk alleles, many of which regulate immune function and relate to variation in gut microbiota β-diversity. We hypothesized ethnically distinct UC patients exhibit discrete gut microbiotas with unique luminal metabolic programming that influence adaptive immune responses and relate to clinical status. Using parallel bacterial 16S rRNA and fungal ITS2 sequencing of fecal samples (UC n=30; healthy n=13), we corroborated previous observations of UC-associated depletion of bacterial diversity and demonstrated significant gastrointestinal expansion of Saccharomycetales as a novel UC characteristic. We identified four distinct microbial community states (MCS 1-4), confirmed their existence using microbiota data from an independent UC cohort, and show they co-associate with patient ethnicity and degree of disease severity. Each MCS was predicted to be uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of metabolic products from these pathways. Using a novel in vitro human DC/T-cell assay we show that DC exposure to patient fecal water led to MCS -specific changes in T-cell populations, particularly the Th1:Th2 ratio, and that patients with the most severe disease exhibited the greatest Th2 skewing. Thus, based on ethnicity, microbiome composition, and associated metabolic dysfunction, UC patients may be stratified in a clinically and immunologically meaningful manner, providing a platform for the development of FMC-focused therapy. Fecal microbiome was assessed with Affymetrix PhyloChip arrays from patients with ulcerative colitis and healthy controls.
Project description:High-calorie diets lead hepatic steatosis and to the development of non-alcoholic fatty liver disease (NAFLD), which can evolve over many years into the inflammatory form non-alcoholic steatohepatits (NASH) posing a risk for the development of hepatocellular carcinoma (HCC). Due to the diet and the liver alteration, the axis between liver and gut is disturbed, resulting in gut microbiome alterations. Consequently, detecting these gut microbiome alterations repre-sents a promising strategy for early NASH and HCC detection. We analyzed medical parame-ters and the fecal metaproteome of 19 healthy controls, 32 NASH, and 29 HCC patients target-ing the discovery of diagnostic biomarkers. Here, NASH and HCC resulted in increased in-flammation status and shifts within the composition of the gut microbiome. Increased abun-dance of kielin/chordin, E3 ubiquitin ligase, and nucleophosmin 1 represented valuable fecal biomarkers indicating disease-related changes in the liver. Whereas a single biomarker failed to separate NASH and HCC, machine learning-based classification algorithms provided 0.86% accuracy in distinguishing between controls, NASH, and HCC. Conclusion: Fecal metaproteomics enables early detection of NASH and HCC by providing single biomarkers and ma-chine learning-based metaprotein panels.