The Human Microbiota: Trillions of Your Closest Friends
Justin Cross
Friday, June 19, 2015
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Chapters
Introduction
The Human Microbiota: Trillions of Your Closest Friends
The Composition of the Human Microbiota Varies In Different Tissue Sites
The Composition of the Human Microbiome Changes With Age, Diet and Disease
Changes in the Microbiota Are Associated With IBD and Other Diseases
Clostridium difficile infection
16S ribosomal gene sequencing
Antibiotics induce distinct changes to C. difficile infection resistance and intestinal microbiota composition
Clostridium scindens
Bile acids
Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
Metabolomics workflow for analysis of fecal samples
Components of the targeted data analysis
Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
A single bile acid-metabolizing organism, or a consortia, could be used as a probiotic to limit recurring C. difficile disease
Workflow for Untargeted Differential Analysis
Accurate mass Q-TOF data allows untargeted analysis of the same data
Maintaining instrument performance and sensitivity
Hierarchical clustering of ~3500 metabolites detected
Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
Compounds restored with C. Scindens transplant, or a consortium of 4 intestinal bacterial isolates
All 16 compounds fall into a small group of 26 compounds on the clustered heat map, and this includes the secondary bile acid DCA
Proton Pump Inhibitor (PPI): Omeprazole
FDA has warned C. difficile infection can be a serious adverse consequence of PPI therapy
Daniel Freedberg – Columbia University Hospital
Targeted bile acid analysis across all 12 patients
There are patient-specific differences that could be related to Omeprazole exposure
Untargeted data mining using the Agilent recursive workflow
There are patient-specific differences that could be related to Omeprazole exposure
Across the whole study 57 entities are significantly associated With exposure to Ompezaole
Proton Pump Inhibitor (PPI): Omeprazole
Omperzole and related metabolites identified from METLIN
Confirming the Identification of Omperzole using pure compound
Confirming the Identification of Omperzole by MS/MS
Harnessing the Microbiota to Treat and Prevent Disease
Genespring / MPP multi-omic correlation analysis
Leukemia patients undergoing allogeneic hematopoietic stem-cell transplant at MSKCC
Acknowledgements
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