Sharing Our Bodies: The Symbiosis of Humans and Our Microbiota

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3 Universidade de São Paulo Brasil Sharing Our Bodies: The Symbiosis of Humans and Our Microbiota Christian Hoffmann, PhD School of Pharmaceutical Sciences Dept. of Food Science and Experimental Nutrition 10/2017

4 The Human Microbiome Data overload <- NGS(sequences) Composed of: Bacteria, Archaea, Eukaryotes and Virus Density: a cells/ml (colon) High number of species present One microbiome to each body part (nose, mouth, intestine, skin etc.) Penn Medicine News. July 02, 2014.

5 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.

6 Symbiosis and Dysbiosis Glendinning and Free. Front. Cell. Infect. Microbiol :24. Bäckhed et al. Cell Host & Microbe (5):

7 In the beggining: In this issue of Science, we have: 3 volunteers Sanger seqs: bacteria 1524 seqs: archaea Diversity of the Human Intestinal Microbial Flora Eckburg et al. Science (5728):

8 With the advent of NGS Van Dirk et al. Trends in Gentics (9):

9 Now 3 to 6 billion reads 25 million reads

10 Co-variation with health/diet/lifestyle 2 cohhorts: N=1106 N= x bigger Normalized to 10K sequences / sample Falony et al. Science (6259):

11 Diversity and Function Bacteria Oral Differences in species composition Intestinal Similarities in metabolic functions Phage? The HMP Consortium. Nature :

12 Diversity: Fungi and Archaea 5 archaea genera 66 fungi genera Hoffmann et al. PLoS One (6): e66019

13 What Influences the Gut Microbiome?

14 What Influences the Gut Microbiome? Environment Host Phenotype Genetics Gut Microbiome Antibiotics Inflammation Diet Faith et al. Science (6038): Muegge et al. Science (6032):

15 Microbiome, Diet e Co-evolution Ley et al. Science (5883):

16 Diet and the Microbiome: the case of Burkina Faso. De Filippo et al PNAS 107:

17 Diet and the Microbiome: the case of Burkina Faso. Burkina Faso Italy De Filippo et al PNAS 107:

18 Microbiome variation: Enterotypes Arumugan et al Nature 473(7346):

19 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):

20 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):

21 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

22 Cardiovascular disease: Atherosclerosis An example of where we are now

23 Cardiovascular disease: Atherosclerosis Risk factors: High cholesterol Obesity Diabetes Etc Wang et a. Nature :57-63.

24 CVD risk N = 1865 Serum levels Wang et al Nature 472:57 63

25 CVD risk TMAO N= year followup What is TMAO? Tang et al NEJM 368:

26 Atherosclerosis Animal models: Choline Foam cells (macrophage), With and without ABX Wang et a. Nature :57-63.

27 Atherosclerosis Wang et a. Nature :57-63.

28 Atherosclerosis Microbiome metabolism influences: Example: Choline/Carnitine -> TMA-> TMAO -> Atherosclerosis Koeth et al. (2013). Nat Med. 19(5):

29 Atherosclerosis Many bacterial genes with the same function Rath et al. (2017). Microbiome. 5:54.

30 Archaeobiotic X Atherosclerosis Methanomassiliicoccus luminyensis Methanogenic Intestinal isolate Can grow using TMA producing methane [TMA] - TMA with H2 [TMA] - TMA w/out H2 M.lum. Growth with TMA / H2 M.lum. Growth w/out TMA / H2 Brugere et al. Gut Microbes (1):5-10.

31 Archaeobiotic X Atherosclerosis Brugere et al. Gut Microbes (1):5-10.

32 Thanks! Funding Charis Tsevis