Project description:We explore whether a low-energy diet intervention for Metabolic dysfunction-associated steatohepatitis (MASH) improves liver disease by means of modulating the gut microbiome. 16 individuals were given a low-energy diet (880 kcal, consisting of bars, soups, and shakes) for 12 weeks, followed by a stepped re-introduction to whole for an additional 12 weeks. Stool samples were obtained at 0, 12, and 24 weeks for microbiome analysis. Fecal microbiome were measured using 16S rRNA gene sequencing. Positive control (Zymo DNA standard D6305) and negative control (PBS extraction) were included in the sequencing. We found that low-energy diet improved MASH disease without lasting alterations to the gut microbiome.
Project description:Gut microbial profiling of uterine fibroids (UFs) patients comparing control subjects. The gut microbiota was examined by 16S rRNA quantitative arrays and bioinformatics analysis. The goal was to reveal alterations in the gut microbiome of uterine fibroids patients.
Project description:This study demonstrates the usefulness of the API by generating a baseline gut microbiota profile of a healthy population and estimating reference intervals for the functional abundance of manually selected KEGG pathways. API facilitates microbiome research by providing dynamic and customizable tools for estimating reference intervals for gut microbiota functional abundances. Through the API, researchers can rapidly generate gut microbiota functional profiles of healthy populations to use as a baseline for comparison. The API also allows users to manually select specific KEGG pathways and estimate reference intervals for the functional abundance of those pathways. By generating these customized reference intervals, researchers can better understand the expected range of gut microbiota functions in healthy individuals. API enables microbiome studies to go beyond simple taxonomic profiling and delve deeper into the functional potential of gut microbiome communities. In summary, API represents a valuable tool for microbiome researchers that enhances the ability to elucidate connections between gut microbial functions and human health.
Project description:Cognitive impairment (CI) is a prevalent neurological condition characterized deficient attention, causal reasoning, learning and/or memory. Many genetic and environmental factors increase risk for CI, and the gut microbiome is increasingly implicated. However, the identity of gut microbes associated with CI risk, their effects on CI, and their mechanisms of action remain unclear. Here we examine the gut microbiome in response to restricted diet and intermittent hypoxia, known environmental risk factors for CI. Modeling the environmental factors together in mice potentiates CI and alters the gut microbiota. Depleting the microbiome by antibiotic treatment or germ-free rearing prevents the adverse effects of environmental risk on CI, whereas transplantation of the risk-associated microbiome into naïve mice confers CI. Parallel sequencing and gnotobiotic approaches identify the pathobiont Bilophila wadsworthia as enriched by the environmental risk factors for CI and as sufficient to induce CI. Consistent with CI-related behavioral abnormalities, B. wadsworthia and the risk-associated microbiome disrupt hippocampal activity, neurogenesis and gene expression. The CI induced by B. wadsworthia and by environmental risk factors is associated with microbiome-dependent increases in intestinal IFNy-producing Th1 cells. Inhibiting Th1 cells abrogates the adverse effects of both B. wadsworthia and environmental risk factors on CI. Together, these findings identify select gut bacteria that contribute to environmental risk for CI in mice by promoting inflammation and hippocampal dysfunction.
Project description:The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. In our study, we compared fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was firstly used to characterize bacterial gut microbial communities and related functional change in AT group. We found that the diversity and structure of the microbial community in AT group were significantly changed compared to that of BT group and H group. AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of gut microbiome with functional alteration. There were different KEGG pathways such as downregulated cardiovascular diseases pathway and upregulated infectious diseases in AT group. By metagenomic analysis, metabolic functional pathway was changed after secukinumab therapy. It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.
Project description:The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. In our study, we compared fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was firstly used to characterize bacterial gut microbial communities and related functional change in AT group. We found that the diversity and structure of the microbial community in AT group were significantly changed compared to that of BT group and H group. AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of gut microbiome with functional alteration. There were different KEGG pathways such as downregulated cardiovascular diseases pathway and upregulated infectious diseases in AT group. By metagenomic analysis, metabolic functional pathway was changed after secukinumab therapy. It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.
Project description:Gut microbiota dysbiosis characterizes systemic metabolic alteration, yet its causality is debated. To address this issue, we transplanted antibiotic-free conventional wild-type mice with either dysbiotic (“obese”) or eubiotic (“lean”) gut microbiota and fed them either a NC or a 72%HFD. We report that, on NC, obese gut microbiota transplantation reduces hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-transplanted mice. Of note, this phenotype is blunted in conventional NOD2KO mice. By contrast, lean microbiota transplantation did not affect hepatic gluconeogenesis. In addition, obese microbiota transplantation changed both gut microbiota and microbiome of recipient mice. Interestingly, hepatic gluconeogenesis, PEPCK and G6Pase activity were reduced even once mice transplanted with the obese gut microbiota were fed a 72%HFD, together with reduced fed glycaemia and adiposity compared to non-transplanted mice. Notably, changes in gut microbiota and microbiome induced by the transplantation were still detectable on 72%HFD. Finally, we report that obese gut microbiota transplantation may impact on hepatic metabolism and even prevent HFD-increased hepatic gluconeogenesis. Our findings may provide a new vision of gut microbiota dysbiosis, useful for a better understanding of the aetiology of metabolic diseases. all livers are from NC-fed mice only.
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:The relationship between retinal disease, diet, and the gut microbiome has shown increasing importance over recent years. In particular, high-fat diets (HFDs) are associated with development and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy. However, the complex, overlapping interactions between diet, gut microbiome, and retinal homeostasis are poorly understood. Using high-throughput RNA-sequencing (RNA-seq) of whole retinas, we compare the retinal transcriptome from germ-free (GF) mice on a regular diet (ND) and HFD to investigate transcriptomic changes without influence of gut microbiome. After correction of raw data, 53 differentially expressed genes (DEGs) were identified, of which 19 were upregulated and 34 were downregulated in GF-HFD mice. Key genes involved in retinal inflammation, angiogenesis, and RPE function were identified. Enrichment analysis revealed that the top 3 biological processes affected were regulation of blood vessel diameter, inflammatory response, and negative regulation of endopeptidase. Molecular functions altered include endopeptidase inhibitor activity, protease binding, and cysteine-type endopeptidase inhibitor activity. Human and mouse pathway analysis revealed that the complement and coagulation cascades are significantly affected by HFD. This study demonstrates novel data that diet can directly modulate the retinal transcriptome independently of the gut microbiome.