Project description:Dysbiotic configurations of the human gut microbiota have been linked with colorectal cancer (CRC). Human small non-coding RNAs are also implicated in CRC and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis but their role is less explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens of patients with CRC, or adenomas, and healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We reported a considerable overlap and correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. Furthermore, we identified a combined predictive signature composed by 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC from healthy and adenoma samples (AUC= 0.87). In summary we reported evidence that host-microbiome dysbiosis in CRC can be observed also by altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more accurate tools for diagnostic purposes.
Project description:Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit long term use. In the current study using a chronic morphine-murine model a longitudinal approach was undertaken to investigate the role of morphine modulation of gut microbiome as a mechanism contributing to the negative consequences associated with opioids use. The results revealed a significant shift in the gut microbiome and metabolome within 24 hours following morphine treatment when compared to placebo. Morphine induced gut microbial dysbiosis exhibited distinct characteristic signatures profiles including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance. Collectively, these results reveal opioids-induced distinct alteration of gut microbiome, may contribute to opioids-induced pathogenesis. Therapeutics directed at these targets may prolong the efficacy long term opioid use with fewer side effects.
Project description:Intestinal microorganisms impact on health maintaining gut homeostasis and shaping the host immunity, while gut dysbiosis associates with many conditions including autism, a complex neurodevelopmental disorder with multifactorial aetiology. In autism, gut dysbiosis correlates with symptom severity and is characterized by a reduced bacterial variability and a diminished beneficial commensal relationship. Microbiota can influence the expression of host microRNAs that, in turn, regulate the growth of intestinal bacteria by means of bidirectional host-gut micro-biota cross-talk. We investigated possible interactions among intestinal microbes and between them and host transcriptional modulators in autism. To this purpose, we analysed, by “omics” technologies, faecal microbiome, mycobiome and small non-coding-RNAs (particularly miRNAs and piRNAs) of children with autism and neurotypical development. Patients displayed gut dysbiosis, related to a reduction of healthy gut micro- and mycobiota, and up-regulated tran-scriptional modulators. The targets of dysregulated non-coding-RNAs are involved in intestinal permeability, inflammation and autism. Furthermore, microbial families, underrepresented in patients, participate to the production of human essential metabolites negatively influencing the health condition. Here, we propose a novel approach to analyse faeces as a whole and, for the first time, we detected miRNAs and piRNAs in faecal samples of patients with autism.
Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome. The results were used to demonstarte the usefulness of applying HuMiChip to human microbiome studies.
Project description:Intervention1: NIL: NIL
Control Intervention1: NIL: NIL
Primary outcome(s): 1). Comparative difference in gut microbial signatures in healthy individuals, colorectal (CRC) and ulcerative colitis (UC) patients using BugSpeaks microbiome analytical platform
2). Comparative difference in stool metabolites in healthy individuals, CRC and UC patients
Timepoint: Screening Visit (Up to day 3) Baseline Visit- Day 0
Project description:The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. Here, we apply an integrative approach to combine comprehensive faecal virome, microbiome and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children. We show strong age and antibody related effects across the datasets. Mastadenovirus infection was associated with profound functional changes in the faecal metaproteome. Multiomic factor analysis modelling revealed proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. These findings demonstrate functional remodelling of the gut microbiota accompanies both islet autoimmunity and viral infection.
Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome.
Project description:We report the association between CpG islander methylator phenotype (CIMP) and the gut microbiome in human colorectal cancer tumor and adjacent normal tissue.
Project description:We report the association between CpG islander methylator phenotype (CIMP) and the gut microbiome in human colorectal cancer tumor and adjacent normal tissue.
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.