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PROVIDER: PRJNA1286128 | ENA |
REPOSITORIES: ENA
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Project description:Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of the gram-positive pathogenic and reduction of bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. In this study, we establish a link between the two phenomena, namely gut barrier compromise and dysregulated bile acid metabolism. We show for the first time that morphine fosters significant gut microbial dysbiosis and disrupts cholesterol/bile acid metabolism. Changes in the gut microbial composition is strongly correlated to disruption in host inflammatory homeostasis13,14 and in many diseases (e.g. cancer/HIV infection), persistent inflammation is known to aid and promote the progression of the primary morbidity. We show here that chronic morphine, gut microbial dysbiosis, disruption of cholesterol/bile acid metabolism and gut inflammation; have a linear correlation. This opens up the prospect of devising minimally invasive adjunct treatment strategies involving microbiome and bile acid modulation and thus bringing down morphine-mediated inflammation in the host.
2016-06-01 | E-MTAB-3722 | biostudies-arrayexpress
Project description:Morphine causes microbial dysbiosis. In this study we focused on restoration of native microbiota in morphine treated mice and looked at the extent of restoration and immunological consequences of this restoration. Fecal transplant has been successfully used clinically, especially for treating C. difficile infection2528. With our expanding knowledge of the central role of microbiome in maintenance of host immune homeostasis17, fecal transplant is gaining importance as a therapy for indications resulting from microbial dysbiosis. There is a major difference between fecal transplant being used for the treatment of C. difficile infection and the conditions described in our studies. The former strategy is based on the argument that microbial dysbiosis caused by disproportionate overgrowth of a pathobiont can be out-competed by re-introducing the missing flora by way of a normal microbiome transplant. This strategy is independent of host factors and systemic effects on the microbial composition. Here, we show that microbial dysbiosis caused due to morphine can be reversed by transplantation of microbiota from the placebo-treated animals.
2016-06-01 | E-MTAB-3723 | biostudies-arrayexpress
Project description:Circulating microbiome in cardiovascular diseases
| PRJNA182287 | ENA
Project description:Background: Hypertension is one of the most common metabolic diseases in the elderly and its pathogenesis is associated with microbiota dysbiosis. Recent evidence suggests that oral microbiota dysbiosis is also an important factor in the development of hypertension. However, the relationship between hypertension and oral flora in the elderly has not been adequately investigated. Objective: The aim of this cross-sectional study was to investigate the structure of the oral microbiota and its correlation with hypertension in elderly hypertensive patients. To provide new ideas for the prevention and treatment of hypertension. Methods: 206 subjects aged 60 ~ 89 years were selected and divided into normal (CON) and hypertensive (HTN) groups, according to the 2018 Chinese Guidelines for the Management of Hypertension. The oral microbiome composition of saliva samples was determined by 16S rRNA gene sequencing. Results: Although there was no significant difference in α and β diversity between the two groups, systolic and diastolic blood pressure were the most important factors influencing the structure of the oral microbiota. At the phylum level, the relative abundance of the spirochete phylum and the mutualistic bacterial phylum was higher in the HT group than in the CON group (p < 0.05). Diastolic blood pressure was negatively correlated with Streptococcus. Furthermore, we analyzed HTN patients with 120 mmHg<systolic blood pressure<160 mmHg and systolic blood pressure>160 mmHg separately and found that the abundance of Saccharibacteria_(TM7) was significantly increased in the HTN_2 group. Conclusions: Our study identified specific oral microbiota in elderly hypertensive patients, confirming the relationship between oral microbiota and hypertension. This enhances our understanding of the important role of oral microbiota in the pathogenesis of hypertension and accumulates more evidence for microbial involvement in the development of hypertension.
2024-09-17 | GSE277296 | GEO
Project description:Autoimmune diseases, such as rheumatoid arthritis, are associated with significant gut microbiota dysbiosis. Here we show that remodelling of 24h rhythms within the gut during inflammatory joint disease drives profound changes in the microbiome and gut permeability.
2023-03-15 | GSE184233 | GEO
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.
2020-11-30 | E-MTAB-8739 | biostudies-arrayexpress
Project description:The microbiome plays a significant role in gut brain communication and is linked to several animal and human diseases. Hypertension is characterized by gut dysbiosis, and this study aimed to determine how the gut microbiome differed between male and female normotensive and hypertensive rodents. WKY is a genetic control for spontaneous hypertensive rats or SHR which is well documented to have elevated blood pressure at approximately 8 to 10 weeks. We compared the microbiome of normotensive and hypertensive rodents using a meta-genomics approach.
2023-10-30 | GSE186517 | GEO
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.
2018-04-16 | E-MTAB-5550 | biostudies-arrayexpress
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.
2014-02-04 | E-GEOD-54290 | biostudies-arrayexpress
Project description:Cervicovaginal microbiome dysbiosis is associated with increased prevalence and incidence of sexually transmitted infections including HIV. We compared the cervicovaginal proteome as characterised by mass-spectrometry of four groups of African female sex workers (total N=50) grouped by microbiome composition as characterised by 16S rDNA microarray. Group 1 had a Lactobacillus crispatus-dominated microbiome, group 2 a L. iners-dominated microbiome, and groups 3 and 4 had a microbiome containing multiple genera of anaerobic bacteria, with group 3 representing transition to or from dysbiosis and group 4 full dysbiosis. 82 human proteins were differentially abundant among the groups, either showing an increasing or decreasing trend from microbiome groups 1 to 4. Proteins that increased included proteasome subunits and other proteins involved in catabolic metabolism, actin organising proteins and proteins involved in the immune response. Proteins that decreased included antiproteases, keratins, and cornified envelope proteins. We also compared the abundance of pre-defined proteins of interest among microbiome groups: markers of cell type, inflammation, and cell death, and mucins. The dysbiotic groups had increased abundance of proteins unique to lymphocytes and macrophages, pro-inflammatory cytokines, cell death markers, and MUC5B. We conclude that the cervicovaginal human proteome is associated with the cervicovaginal microbiome in a dose-response manner. The changes are likely caused by a pro-inflammatory influx of immune cells and an increase of cell death in dysbiosis. Dysbiosis-associated immune activation, breaches in epithelial integrity, altered mucin balance, and altered protease-antiprotease balance may all contribute to the increased risk of HIV transmission when cervicovaginal dysbiosis is present.
2015-09-25 | PXD001435 | Pride