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:The gut microbiome plays an important role in normal immune function and has been implicated in several autoimmune disorders. Here we use high-throughput 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=61) and healthy controls (n=43). Alterations in the gut microbiome in MS include increases in the genera Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signaling and NF-kB signaling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of the genera Prevotella and Sutterella, and decreased Sarcina, compared to untreated patients. MS patients of a second cohort show elevated breath methane compared to controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.
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.
Project description:In a prior report, we observed two distinct lung microbiomes in healthy subjects that we termed â??pneumotypesâ??: pneumotypeSPT, characterized by high bacterial load and supraglottic predominant taxa (SPT) such as the anaerobes Prevotella and Veillonella; and pneumotypeBPT, with low bacterial burden and background predominant taxa (BPT) found in the saline lavage and bronchoscope. Here, we determined the prevalence of these two contrasting lung microbiome types, in a multi-center study of healthy subjects. We confirmed that a lower airway microbiome enriched with upper airway microbes (pneumotypeSPT) was present in ~45% of healthy individuals. Cross-sectional Multicenter cohort. BAL of 49 healthy subjects from three cohort had their lower airway microbiome assessed by 16S rDNA sequencing and microbial gene content (metagenome) was computationally inferred from taxonomic assignments. The amplicons from total 100 samples are barcoded; the barcode and other clinical characteristics (e.g. inflammatory biomarkers and metabolome data) for each sample are provided in the 'Pneumotype.sep.Map.A1.txt' file.
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.
Project description:A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.
Project description:The human gut is colonized by trillions of microorganisms that influence human health and disease through the metabolism of xenobiotics, including therapeutic drugs and antibiotics. The diversity and metabolic potential of the human gut microbiome have been extensively characterized, but it remains unclear which microorganisms are active and which perturbations can influence this activity. Here, we use flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the human gut contains distinctive subsets of active and damaged microorganisms, primarily composed of Firmicutes, which display marked temporal variation. Short-term exposure to a panel of xenobiotics resulted in significant changes in the physiology and gene expression of this active microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding novel candidate proteins for antibiotic resistance, drug metabolism, and stress response. These results demonstrate the power of moving beyond DNA-based measurements of microbial communities to better understand their physiology and metabolism. RNA-Seq analysis of the human gut microbiome during exposure to antibiotics and therapeutic drugs.