Project description:Transcriptome analysis of partially degraded and fragmented RNA samples from mus musculus gut Global gene expression profiling has shown the gut transcripts changes through administration of aspirin while probiotics strain administration beforehand attenuates the effect more than teprenone.
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.
Project description:Transcriptome analysis of partially degraded and fragmented RNA samples from mus musculus gut Global gene expression profiling has shown the gut transcripts changes through administration of aspirin while probiotics strain administration beforehand attenuates the effect more than teprenone. We analyzed five groups of mice gut using the Affymetrix Mouse Gene 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No techinical replicates were performed.
Project description:Background: The long-term high-fat, high-sugar diet exacerbates type 2 diabetes mellitus (T2DM)-related cognitive impairments. The negative impact of poor dietary patterns on brain development and neurological function may be related to gut microbiota disturbance. The role of phlorizin in mitigating glucose and lipid metabolism disorders is well documented. However, the protective effect of phlorizin on diabetes-related cognitive dysfunction is unclear. Therefore, the present study aimed to investigate the effect of dietary supplementation of phlorizin on high-fat and high-fructose diet (HFFD)-induced cognitive dysfunction and evaluate the crucial role of the microbiota-gut-brain axis. Results: Dietary supplementation of phlorizin for 14 weeks effectively prevented glucolipid metabolism disorder, spatial learning impairment, and memory impairment in HFFD mice. In addition, phlorizin improved the HFFD-induced decrease in synaptic plasticity, neuroinflammation, and excessive activation of microglia in the hippocampus. Transcriptomics analysis shows that the protective effect of phlorizin on cognitive impairment was associated with increased expression of neurotransmitters and synapse-related genes in the hippocampus. Phlorizin treatment alleviated colon microbiota disturbance, mainly manifested by an increase in gut microbiota diversity and the abundance of short-chain fatty acid (SCFA)-producing bacteria. The level of microbial metabolites, including SCFA, inosine 5'-monophosphate (IMP), and D (-)-beta-hydroxybutyric acid (BHB) were also significantly increased after phlorizin treatment. Moreover, integrating multiomics analysis observed tight connections between phlorizin-regulated genes, microbiota, and metabolites. Furthermore, removal of the gut microbiota via antibiotics treatment diminished the protective effect of phlorizin against HFFD-induced cognitive impairment, underscoring the critical role of the gut microbiota in mediating cognitive behavior. Importantly, supplementation with SCFA and BHB alone mimicked the regulatory effects of phlorizin on cognitive function. Conclusions: These results indicate that gut microbiota and their metabolites mediate the ameliorative effect of phlorizin on HFFD-induced cognitive impairment. Therefore, phlorizin can be used as an easy-to-implement nutritional therapy to prevent and alleviate metabolism-related neurodegenerative diseases by targeting the regulation of the microbiome-gut-brain axis.
Project description:Obesity and overweight are closely related to diet, and gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating the human gut microbiome. A randomized, double-blind, placebo-controlled study was conducted on 72 overweight individuals. Over a 12-week period, probiotic groups consumed 5×10^9 colony-forming units of HY7601 and KY1032), whereas the placebo group consumed the same product without probiotics. After treatment, the probiotic group displayed a reduction in body weight (p <0.001), visceral fat mass (p <0.025), and waist circumference (p <0.007), and an increase in adiponectin (p <0.046), compared with the placebo group. Additionally, HY7601 and KY1032 supplementation modulated bacterial gut microbiota characteristics and beta diversity by increasing Bifidobacteriaceae and Akkermansiaceae, and decreasing Prevotellaceae and Selenomonadaceae. In summary, HY7601 and KY1032 probiotics exert anti-obesity effects by regulating the gut microbiota; hence, they have therapeutic potential for preventing or alleviating obesity and overweight.
Project description:The understanding of the effects of compounds on the gut microbiome is limited and in particular we don’t know whether structurally similar compounds have similar or distinct effects on the gut microbiome. Here we selected berberine (BBR), an isoquinoline quaternary alkaloid, and sixteen structural analogues, and evaluated their effects on in vitro cultured individual gut microbiomes. The responses of the individual microbiomes were evaluated by metaproteomic profiles and by assessing butyrate production. BBR and eight analogues led to changes in proteins involved in microbial defense and stress responses, and enrichment of proteins from Verrumicrobia, Proteobacteria and Bacteroides phyla. It also led to a decrease in proteins from the Firmicutes phylum and its Clostridiales order which correlated to decrease proteins involved in the butyrate production pathway and butyrate concentration. Three of the compounds, Sanguinarine, Chelerythrine and Ethoxysanguinarine activated bacterial protective mechanisms, enriched Proteobacteria, increased opacity proteins and markedly reduced butyrate production. Dihydroberberine had a similar function to BBR in enriching the Akkermansia genus. In addition, it showed less overall adverse impacts on the functionality of the gut microbiome, including a better maintenance of the butyrate level. Our study shows that ex vivo microbiome assay can assess differential regulating effects of compounds with subtle differences and reveals that compound analogues can have distinct effects on the microbiome.
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.
Project description:Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline. Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome. Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.
Project description:Transcriptional profiling of mouse gut wall tissue following infection with Salmonella or treatment with Probiotics to see the role of probiotics in preventing salmonella infection through gut mucosal route of mouse.
Project description:"Here, we studied well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, N=1,106, Belgium) and the effect of environments on microbiome."