Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883240 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. RNA-Seq analysis of the human gut microbiome during consumption of a plant- or animal-based diet.
2013-12-05 | E-GEOD-46761 | biostudies-arrayexpress
Project description:Opioids such as morphine have many beneficial properties as analgesics, however, opioids may induce multiple adverse gastrointestinal symptoms. We have recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. However, it is unclear how opioids modulate the gut homeostasis. By using a mouse model of morphine treatment, we studied effects of morphine treatment on gut microbiome. We characterized phylogenetic profiles of gut microbes, and found a significant shift in the gut microbiome and increase of pathogenic bacteria following morphine treatment when compared to placebo. In the present study, wild type mice (C57BL/6J) were implanted with placebo, morphine pellets subcutaneously. Fecal matter were taken for bacterial 16s rDNA sequencing analysis at day 3 post treatment. A scatter plot based on an unweighted UniFrac distance matrics obtained from the sequences at OTU level with 97% similarity showed a distinct clustering of the community composition between the morphine and placebo treated groups. By using the chao1 index to evaluate alpha diversity (that is diversity within a group) and using unweighted UniFrac distance to evaluate beta diversity (that is diversity between groups, comparing microbial community based on compositional structures), we found that morphine treatment results in a significant decrease in alpha diversity and shift in fecal microbiome at day 3 post treatment compared to placebo treatment. Taxonomical analysis showed that morphine treatment results in a significant increase of potential pathogenic bacteria. Our study shed light on effects of morphine on the gut microbiome, and its role in the gut homeostasis.
2018-04-16 | E-MTAB-5546 | biostudies-arrayexpress
Project description:Although obesity is a modifiable risk factor for pancreatic cancer, the role of dietary changes that lead to weight loss in pancreatic carcinogenesis remains unknown. Thus, we determined the effects of weight normalization via dietary switch on pancreatic carcinogenesis and the associated mechanisms. Five-week-old male and female LSL-KrasG12D/+; p48Cre/+ (KC) mice (8-12/diet group/sex) were fed a high-fat, diet-induced obesity diet (DIO; 60 kCal% energy from fat) or a low-fat, control diet (CD; 11 kCal% energy from fat) for 21 weeks. A subset of mice was fed the DIO for 8 weeks, then switched to a CD for 13 additional weeks (DIO→CD). Cancer incidence was evaluated by histology. Lipidomics and RNAseq followed by bioinformatic analysis were conducted to identify possible mechanisms. The gut microbiome was characterized using 16s rRNA amplicon sequencing. After 21 weeks, DIO-fed mice had significantly higher body weight, fat mass, and pancreatic acinar-to-ductal metaplasia compared to the other 2 groups. While none of the 21 mice fed a CD developed cancer, 2 out of 21 DIO-fed mice did. Switching from a DIO to a CD normalized body weight and composition, reduced acinar-to-ductal metaplasia and prevented cancer incidence with no mice developing cancer. Mechanistically, the DIO affected the expression of genes regulating cellular metabolism, immune function, and cell-signaling, while CD and DIO→CD had similar global gene expression. Moreover, DIO increased epoxy metabolites of linoleic acid, which were mitigated by the dietary switch. Finally, compared to a CD, DIO altered the gut microbiome and switching from a DIO to a CD restored the gut microbiome profile to one close to the mice fed a CD. Body weight normalization mitigates obesity-accelerated pancreatic carcinogenesis, in part, by affecting inflammatory and cell signaling pathways, reducing epoxy metabolites, and modulating the gut microbiome.
2025-08-30 | GSE293790 | 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:Polyphenols are promising therapeutics for Crohn’s disease (CD), yet their bioavailability is largely dependent on the gut microbiome. The bioactive metabolites, metabolic pathways, and anti-inflammatory mechanisms underlying their effects remain poorly defined. Through integrated multi-omics and dietary analysis, we identified hippuric acid as a reduced metabolite in CD patients and a biomarker of polyphenol–microbiome interactions. We further demonstrate that hydrocinnamic acid, derived from microbiome metabolism of dietary trans-cinnamic acid and subsequently converted to hippuric acid by the host, ameliorates colitis in mice via the PPAR-γ pathway. Notably, we identified Bifidobacterium breve Bbr60 and Escherichia coli FAH as novel hydrocinnamic acid producers, complementing the established pathway in Clostridium sporogenes and suggesting additional microbial contributors. Collectively, our findings establish hydrocinnamic acid as a diet-dependent, colon-produced, mild PPAR-γ agonist with the potential to minimize adverse effects associated with traditional PPAR-γ agonists. This work establishes a foundation for developing microbiota-targeted, polyphenol-based therapeutic strategies for CD patients.
2025-09-22 | GSE308767 | GEO
Project description:The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here we profiled the gut microbiome in a discovery (n=1011) and validation (n=484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status.
| EGAS00001004480 | EGA