Microbiota, Diet and Health
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1 Universidade de São Paulo Brasil Microbiota, Diet and Health Christian Hoffmann USP/FCF November 2016
2 The Human Microbiome Composed of : Bacteria, Archaea, Eukaryotes e Viruses Density: a cells/ml (colon) High number of species present Distinct compositions for each body site (nose, mouth, intestine, skin etc.) Charis Tsevis
3 The Human Microbiome Composed of : Bacteria, Archaea, Eukaryotes e Viruses Density: a cells/ml (colon) High number of species present Distinct compositions for each body site (nose, mouth, intestine, skin etc.) Costello et al. Science (5960):1694:1697.
4 Symbiosis and Dysbiosis Glendinning and Free. Front. Cell. Infect. Microbiol :24. Bäckhed et al. Cell Host & Microbe (5):
5 Diversity Differences in species composition Oral Overall similarities in metabolic functions Intestinal The HMP Consortium. Nature :
6 Diversity: Fungi and Archaea 5 archaea genera 66 fungi genera Hoffmann et al. PLoS One (6): e66019
7 Determinants of Gut Microbiome Composition Environment Host Phenotype Genetics Gut Microbiome Antibiotics Inflammation Diet
8 Microbiome, Diet e Co-evolution Ley et al. Science (5883):
9 Diet and the Microbiome: the case of Burkina Faso. De Filippo et al PNAS 107:
10 Diet and the Microbiome: the case of Burkina Faso. Burkina Faso Italy De Filippo et al PNAS 107:
11 Microbiome variation: Enterotypes Arumugan et al Nature 473(7346):
12 C.4022 C.3027 C.3029 C.3085 C.3082 C.3079 C.3032 C.3057 C.3013 C.3063 C.4006 C.4025 C.4021 C.3022 C.3067 C.4013 C.4024 C.4010 C.3037 C.3042 C.3015 C.4009 C.3056 C.3020 C.3083 C.3010 C.3041 C.3051 C.3075 C.3023 C.3084 C.3066 C.3053 C.3060 C.4002 C.4027 C.3044 C.3071 C.4020 C.4011 C.3025 C.3048 C.3004 C.3007 C.3016 C.3034 C.4023 C.3047 C.3059 C.3039 C.4028 C.3049 C.4005 C.3019 C.3050 C.3030 C.3072 C.3009 C.3070 C.3045 C.3006 C.3001 C.3008 C.3046 C.4001 C.3074 C.3055 C.3086 C.3078 C.3062 C.3076 C.4004 C.3043 C.4017 C.3031 C.3033 C.4007 C.4030 C.4026 C.3018 C.3038 C.3081 C.3011 C.3068 C.3017 C.4000 C.4014 C.3014 C.3026 C.3080 C.3064 C.3052 C.3028 C.3003 C.4029 C.3040 Percent of Total Sequences Microbiome variation: Enterotypes A balance between Bacteroides e Prevotella Prevotella% Bacteroides% Arumugan et al Nature 473(7346):
13 Methionine Leucine Valine Lysine Tyrosine Serine Histidine Isoleucine Taurine Glutamate Proline Phenylalanine Threonine Alanine Asparate Hydroxyproline Glycine Arginine Tryptophan Cystine Protein Animal Protein Dairy Protein Choline, Sphingomyelin Choline, Phosphatidylcholine w/o suppl. Choline, Phosphatidylcholine Sum of Betaine & Choline Total Choline, no betaine Choline w/o suppl. Choline, Glycerophosphocholine Cholesterol Animal fat Long Chain N3 Fatty Acid no vit. pills Long Chain N3 Fatty Acid Omega 3,no alpha linolenic acid Long Chain Fatty Acid nosuppl. Gamma Linolenic fatty acid Long Chain Fatty Acid Docosahexaenoic fatty acid (DHA) Arachadonic fatty acid Palmitoleic fatty acid Gamma linolenic fatty acid c9,t11 conjug diene isomer 18:2 Linoleic Calcium Vitamin D w/o vit. pills Phosphorous w/o suppl. Zinc w/o vit. pills Dairy Vitamin D Vitamin B12 w/o vit. pills Lactose Germ Scores Fructose Carbohydrates Glucose Sucrose Enterotypes and human diet Enterotype 1 (Bacteroides) Enterotype 2 (Prevotella) Dairy Calcium Color Key Global associations with usual diet, not with recent diet Wu et al Science 334(6052):
14 Ruminococcaceae unkgen Anaerovorax Prevotella Prevotellaceae unkgen Candida Streptococcus Anaerofustis Pichia Alternaria Coprococcus Anaerotruncus Oxalobacter Ruminococcus Aspergillus Actinomyces Meyerozyma Gemella Lachnospiraceae unkgen Clostridiaceae unkgen Turicibacter Dorea Bryantella Coprobacillus Lachnospira Bacteroides Microbiome fungi and usual diet r Key lue *** *** * ** *** *** ** ** ** * *** *** ** ** *** * **** *** *** * *** **** *** ** **** *** ** *** **** c05_carbohydrates c11_pufa c04_vegetablefat c14_animalprot c02_aminoacids c12_choline fung/bact_usual Spearman Correlation Color Key Value Hoffmann et al. PLoS One (6): e66019 *** ***
15 Cladosporium Aspergillus Dialister IncertaeSedisXII unkgen Catenibacterium Ruminococcus Candida Xylanibacter Prevotella Prevotellaceae unkgen Ruminococcaceae unkgen Sutterella Porphyromonadaceae unkgen Alternaria Coprobacillus Granulicatella Bryantella Anaerotruncus Anaerofustis Eggerthella Bacteroides Clostridiaceae unkgen Actinomyces Peptostreptococcaceae unkgen Syntrophococcus Fusobacterium TM7_genera_incertae_sedis Parabacteroides Lachnospira Lachnospiraceae unkgen Lachnobacterium Roseburia Ascomycota phylum Coprococcus Microbiome fungi and recent diet ey 0.2 ** ** * * * * * **** ** *** **** **** ** * **** *** * ** * ** * c03_totalcarb_totalsugars c01_glycemicload c06_alcohol_h2o_caf_vitak c05_totsolinsolfib_vegprot c14_glycemicindex c08_totalsatfa_cla c13_shortchainfa Spearman Correlation Color Key Value Hoffmann et al. PLoS One (6): e66019 *** ***
16 Population variation Lozupone et al. Nature : Gomez et al Cell Reports 14(9): Martinez et al Cell Reports 11(4): Schnor et al Nature Communications 5:3654 Clemente et al Science Advances 1(3):e
17 So What? Who cares?
18 Manipulating the Gut Microbiome 4D Pharma, AOBiome, APC Microbiome Institute, AbbVie, ActoGeniX, Admera Health, Advanced Technology Ventures, Advancing Bio, AgBiome, Assembly Biosciences, Avid Biotics, Azitra, BioAster Technology Research Institute, BioBalance Corporation, BioConsortia, BioGaia, Biocartis, Biomecite Diagnostics, C3 Jian, Center for Biologics Evaluation and Research (CBER), Cipac Therapeutics, Companion PBx, Concorde Medical Group, Da Volterra, Dairy Innovation Australia Limited (DIAL), Danisco, Debiopharm, Dermala, Enso Ventures, Enterologics, Enterome BioScience, Epibiome, Epiva Therapeutics, Evelo Therapeutics, Evolve Biosystems, Evotec, ExeGi Pharma, FUJIFILM Diosynth Biotechnologies, Flagship Ventures, GMU Microbiome Analysis Center (MBAC), GT Biologics, Gallinee, Genetic Analysis, Genewiz, Gustave Roussy, Human Longevity, Hy Laboratories, Igen Biotech Group, Illumina Accelerator, Immune Biologics, Immuron, Inocucor Technologies, Inserm, Institut Merieux, Intrexon, Janssen, Johnson & Johnson Innovation Center, KOLUPOHAKU TECHNOLOGIES (KPT), Kindstar Global, Lundbeckfond Ventures, MBcure, MaaT Pharma, Manzo Pharmaceuticals, Matatu, Merck, Metabiomics, Metabogen, Metabolon, Metanome, Metrodora Therapeutics, MiOmics, MicroBiome Therapeutics, Microbiome, Microbiome Diagnostics, Microbiota Company, Miyarisan Pharmaceutical, Monarch Labs, Morgenthaler, MyBiotics, NIZO Food Research, Novartis, OmniBiome Therapeutics, One Way Liver, OpenBiome, OptiBiotix Health, Oragenics, Osel, OxThera, Pfizer, Pivot Bio, Prev AbR, Procarta Biosystems, PureFlora, Quorum Innovations, Rebiotix, Ritter Pharmaceuticals, Second Genome, Sen Nuo Wei Biotechnology, Seres Therapeutics, Servier, Seventure, Shire, Shoreline Biome, SigmaTau Pharmaceuticals, SporeGen, Swecure, Symberix, Symbiota, Symbiotix Biotherapies, Synlogic, Synthetic Biologics, TargEDys, Therapeutic Solutions International, TriPhase Pharmaceuticals, UAS Labs, Universal Stabilisation Technologies, VSL Pharmaceuticals, Vaiomer, Vedanta Biosciences, ViroPharma Incorporated, Vithera Pharmaceuticals, Wavepoint Ventures, Whole Biome, Xycrobe Therapeutics, Yakult Honsha, clecta Microbiome Therapeutics Market to
19 Private Companies Working In The Microbiome Company Description Total Funding (M) C3 Jian Biotech company focusing on diagnosing, treating, and preventing diseases relevant to the human microbiome (with a focus on oral health) $113 Eligo Bioscience Developing ultra-precise antibiotics to target harmful bacteria and sparing beneficial ones Enterome Focusing on microbiome-related diseases such as Irritable Bowel Syndrome and metabolic diseases (diabetes and obesity) $2.2 $23.8 EpiBiome Evelo Therapeutics Evolve BioSystems Vedanta Biosciences Kallyope Rebiotix Second Genome Precision microbiome engineering, creating therapies for humans and $5.7 agriculture without the use of antibiotics Company that seeks to create microbiome therapies for the treatment of cancer $35 Working to develop products that maintain healthy microbiomes in infants $9 Fecal transplantation substitutes $50 Cutting-edge technologies in sequencing, bioinformatics, neural imaging, cellular and molecular biology, and human genetics to provide an understanding of gut-brain biology Creating Microbiota Restoration Therapy to deliver live microbes into intestinal tracts to treat disease Clinical-stage company discovering and developing therapies for microbiome related diseases, focusing on inflammatory bowel disease $44 $30 $43 ubiome Sequences, stores, and analyzes data related to the human microbiome $4.9
20 Manipulating the Gut Microbiome Transfer of Lean and Obese phenotype Fecal transplantation Insertion/reinsertion of specific bacterial groups
21 Transfer of Lean and Obese phenotype LF-HPP diet Ridaura et al. Science (6150):
22 Transfer of Lean and Obese phenotype LoSF-HiFV diet HiSF-LoFV diet Ridaura et al. Science (6150):
23 Manipulating the Gut Microbiome Transfer of Lean and Obese phenotype Fecal transplantation Insertion/reinsertion of specific bacterial groups
24 Fecal transplantation Clostridium difficile infection Diarrhea due to antibiotic use: ~10% of all cases, of those: C. difficile responsible for 20%. Usually hopital acquared infection In the USA : estimated that 12% of all HI are caused by C.diff. As high as 16% mortality rate (1 year after diagnostic)
25 Fecal transplantation Fuentes et al. The ISME Journal (8):
26 Fecal transplantation Vancomycin ( n=13 ) Vancomycin e bowel prep ( n=13 ) Vancomycin, bowel prep and transplantation (n=16 ) Study discontinued because of results on the control group Van Nood et al. NEJM (5):
27 Fecal transplantation Problems Safety Standardization Side effects (?) Alternatives Probiotic
28 Manipulating the Gut Microbiome Lean obese phenotype Fecal transplantation Insertion/reinsertion of specific bacterial groups
29 Insertion of specific bacterial groups Probiotics Protection against C. difficile Protection against allergy
30 Clostridium difficile Mouse model Infection by C. difficile Bacterial consortium protects against infection Buffie et al. Nature 2014.
31 Allergy Mouse model Peanut allergy Antibiotic treatment Microorganism introduction Stefka et a. PNAS (36):
32 Universidade de São Paulo Brasil Obrigado!
33
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