Gut-Brain-Liver-Immunome-Environment Axis

Transcription

1 Gut-Brain-Liver-Immunome-Environment Axis Konkel, Environmental Health Perspectives 121 (9) 2013

2 METABIOME All interaction of host and microbes Concepts on Human Microbiome Analysis of Microbial Communities Systems Biology & Non-Linear Systems The Gut Liver Axis: Metabiomarker

3 Human Microbiome 10 x more prokaryote cells than eukatyotic cells in human body Gut Skin Vagina Mouth Nose Throat Mims et al. Medical Microbiology Textbook (2004)

4 Mucosal Biofilm Biofilms in the normal human large bowel: fact rather than fiction R. Bollinger, A Barbas, E. Bush, S. Lin,W. Parker Gut

5 Homeostasis Immunome to Recognizes Biofilm as Self B. Duerop, S. Vaishnava, and L. Hooper Immunity

6 Disease State Exposure of Immunome to Foreign Antigen B. Duerkop, S. Vaishnava, and L. Hooper Immunity

7 METABIOME All interaction of host and microbes Concepts on Human Microbiome Analysis of Microbial Communities Systems Biology & Non-Linear Systems The Gut Brain Axis: Metabiomarker

8 Ion Torrent PGM (Thermo-Fisher) 4 million reads 10,000 reads / sample

9 >QAMNR:00004:00004 DNA (C) 16S rrna PCR (B) Nucleic Acid Extraction (A) Sample Collection (E) Barcoded Samples (F) NextGen Sequencer CTGATCAGAGAGTTTGATCATGGGCTCAGGATGAACGCTAGCTACAGGGCTTAACACATGCAA GTCGAGGGGCAGCATTTTAGTTTTGCTT >QAMNR:00004:00005 AGTTCGACTAGAGTTTGATCATGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAG TCGAACGAAGCACTTTTATTTGATTTTCTTCGGAATGAAGATTTGTGACTGAGTGGCGGACGGG TGAGTAACGCGTGGGTAACCTGCCTCATACAGGGGGATAACAGTTTGGAAACGCTGCTAAATA CCGCATAAGCGCACAGGGTCGCATGACCTGGGTGTGAAAACTCCGGGTGGGTATGAGATGGG >QAMNR:00004:00006 ATCTCTATAGAGTTTGATCATGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGT CGAGGGGGCAGCATGATTTGAAGCTTTGCTTTCAATTGATGGCGACCGGCGCACGGGGTGAGT AACACGTATCCAACCTGCCGATAACTCGGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGA TAGTATAGTATTTCCGCATGGTTTTCACTATTAAAGAATTTCGGTTTATCGATGGGGATGCGTT CCATTAGATAGTTTGGCGGGGTAACGGCCCACCAAGTCAACGTGGGATAGGGGGTTCTGAGAG GAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGC >QAMNR:00004:00007 CGCACGCTAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGT CGAACGGGGAATATTTATTGAAGCTTTCGGTTGATTTAATTTATTCTAGTGGCGGACGGGGTGA GTAACGCGTGGGTAACCTGCCTTATACTGGGGGATAACAGCCAGAAATGGCTGCTAATCCGAT AAGCGCACAAGAA >QAMNR:00004:00008 AGTCGACTAGAGTTTTGATCATGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAG TCGAGGGGGCAGCATGGTCTTAGCTTGCTAAGGCCGATGGCGACCGGCGCACGGGGTGAGTAA CACGTATCCAACCTGCCGTCTACTCTTGGACAGCCTTCTGAAAGGAAGATTAATACAAGATGG CATCATGAGTTCACATGTTCACATTGATTAAAGGTATTCCGGTAGACGATGGGGATGCGTTCC ATTAGATTAGTAGGCGGGGTAACGGCCCACCTAGTCAACGATGGATAGGGGTTCTGAGAGGAA GGTCCCCACATTGGAACTGAGACACGGCCCAAACTCCTACGGGAGGCAGC >QAMNR:00004:00010 CGTGTGCGAGAGTTGATCCTGGCTCAGGACGAACGCTGGCGCGCGCCTAACACATGCAAGTCG AACGGAGCTTGCACCTCTGAAGTTTTCGGATGGACGAGGTACAAGCTTAGTGGCGAACGGGTG AGTAACACGTGAAGAACCTGCCCTTCAGTGGGGGACAACAGTTGGAAACGACTG >QAMNR:00004:00011 TGTACGTGAGAGTTTGATTCTGGCTCAGGATGAACGCTAGCGGCAGGCCTAACACATGCAAGT TCGAGGGGCATCGGGATTGAAGCTTGCTTCAATTGCCGGCGACCGGCGCACGGGTGCGTAACG CGTATGTAACCTACCTATAACAGGGGCATAACACTGAGAAAATTTGGTACTAA (G) Millions of sequence reads (H) Sequence Clusters = OTUs 8 (I) Taxa Abundance (K) Modeling Non-linear Ecosystem (J) Phylogenetic Tree

10 Metabolome several thousand metabolites GC-MS / LC-MS Data compatability

11 METABIOME Concepts on Human Microbiome Project Analysis of Microbial Communities Systems Biology & Non-Linear Systems The Gut Liver Axis: : Metabiomarker(s)

12 NonLinear Dynamics: Bacteriodes Abundance Sparse Nonparametric data

13 Ecological Oscillations Barcoded Pyrosequencing Reveals That Consumption of Galactooligosaccharides Results in a Highly Specific Bifidogenic Response in Humans Lauren M. G. Davis1, Ine ś Mart ínez1, Jens Walter1, Caitlin Goin2, Robert W. Hutkins1 PLoS ONE Volume 6 Issue 9 e25200

14 Effect of Probiotics in Obese Ossabaw Pigs Pat Gillevet, Masi Sikaroodi, Sean Smith Dept Environmental Science and Policy Dept Bioinformatics and Computational Biology George Mason University, Fairfax, Virginia Gloria Solano-Aguilar, Joe Urban, Harry Dawson Diet, Genomics,and Immumology Lab, USDA George Mason University

15 PCO of Microbiome Lean Diet = Control High Fat Diet = Placebo High Fat Diet + Probiotic = Probiotic PCO case scores (Bray Curtis) Control 0.4 Axis Placebo Probiotic -0.4 Axis 1

16 USDA Porcine Probiotic Study Edge = Correlation between nodes Nodes = Features

17 Pearson s Correlation Analysis Microbiome Liver Adipose Blood Brain Hypothalamus

18 Model Interactions between Components of Metabiome Homeostasis T. MacDonald and G. Monteleone Immunity, Inflammation, and Allergy in the Gut Science 307,

19 Metabiome Concepts on Human Microbiome Project Analysis of Microbial Communities Systems Biology & Non-Linear Systems The Gut Liver Axis: Metabiomarker Knowledge Discovery Biological Plausibility?

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21 Unsupervised Clustering Bacteria PCO case scores (Bray Curtis) Control 0.2 Axis NASH Axis 1 OUTCOMES???

22 LEFSE

23 Machine Learning Supervised Clustering

24 Machine Learning Bacteria + Metabolites Predictions Truth Niave Bayes

25 Machine Learning Niave Validation

26 Summary Sample Integrity Proper OTU selection Data compatability Dynamic Ecosystem Interplay between host and microbiome Microbiome is another organ Nonlinear modeling of system Niave validation of Biomarker