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

c.hoffmann@usp.br

Universidade de São Paulo Brasil

The Human Microbiome

Penn Medicine News. July 02, 2014.

Composed of: Bacteria,

Archaea, Eukaryotes and Virus

Density: 1011 a 1012 cells/mL (colon)

High number of species present

One microbiome to each body part (nose, mouth, intestine, skin etc.)

Data overload <- NGS(sequences)

Costello et al. Science 2009. 326(5960):1694:1697.

The Human Microbiome Composed of :

Bacteria, Archaea, Eukaryotes e Viruses

Density: 1011 a 1012 cells/mL (colon)

High number of species present

Distinct compositions for each body site (nose, mouth, intestine, skin etc.)

Glendinning and Free. Front. Cell. Infect. Microbiol. 2014. 4:24. Bäckhed et al. Cell Host & Microbe 2012. 12(5):611–622.

Symbiosis and Dysbiosis

In this issue of Science, we have:

3 volunteers

Sanger

11831 seqs: bacteria

1524 seqs: archaea

“Diversity of the Human Intestinal Microbial Flora”

Eckburg et al. Science 2005. 308(5728): 1635–1638.

In the beggining:

With the advent of NGS

Van Dirk et al. Trends in Gentics 2014. 30(9):418–426.

Now

3 to 6 billion reads 25 million reads

Co-variation with health/diet/lifestyle

Falony et al. Science 2016. 352(6259): 560-564.

2 cohhorts: N=1106

N=1135

700x bigger

Normalized to 10K sequences / sample

Diversity and Function

Bacteria

Differences in species composition

Similarities in metabolic functions

Phage?

The HMP Consortium. Nature 2012. 486:207–214

Oral

Intestinal

Diversity: Fungi and Archaea

5 archaea genera

66 fungi genera

Hoffmann et al. PLoS One 2013. 8(6): e66019

What Influences the Gut Microbiome?

What Influences the Gut Microbiome?

Diet

Genetics Host Phenotype

Antibiotics Inflammation

Gut Microbiome

Environment

Faith et al. Science 2011. 333(6038):101-104 Muegge et al. Science 2011. 332(6032):970-974

Microbiome, Diet e Co-evolution

Ley et al. Science. 2008 320(5883):1647-1651

Diet and the Microbiome: the case of Burkina Faso.

De Filippo et al. 2010. PNAS 107:14691-14696.

Diet and the Microbiome: the case of Burkina Faso.

Italy

Burkina Faso

De Filippo et al. 2010. PNAS 107:14691-14696.

Microbiome variation: Enterotypes

Arumugan et al. 2011 Nature 473(7346):174-180

Microbiome variation: Enterotypes

A balance between Bacteroides e Prevotella

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Arumugan et al. 2011 Nature 473(7346):174-180

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Enterotype 1

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Enterotypes and human diet

Global associations with usual diet, not with recent diet

Wu et al. 2011 Science 334(6052): 105-108

Population variation

Lozupone et al. Nature 2012. 489:220–230

Gomez et al. 2016. Cell Reports 14(9):2142-2153

Martinez et al. 2015 Cell Reports 11(4):527–538

Schnor et al. 2014. Nature Communications 5:3654

Clemente et al. 2015. Science Advances 1(3):e1500183

Cardiovascular disease: Atherosclerosis

An example of where we are now

Cardiovascular disease: Atherosclerosis

Risk factors:

High cholesterol

Obesity

Diabetes

Etc

Wang et a. Nature 2011. 472:57-63.

CVD risk N = 1865 Serum levels

Wang et al. 2011. Nature 472:57–63

CVD risk

TMAO

N=4007

3 year followup

What is TMAO?

Tang et al. 2013. NEJM 368:1575-1584

Atherosclerosis

Animal models:

Choline

Foam cells (macrophage),

With and without ABX

Wang et a. Nature 2011. 472:57-63.

Atherosclerosis

Wang et a. Nature 2011. 472:57-63.

Atherosclerosis Microbiome metabolism influences:

Example: Choline/Carnitine -> TMA-> TMAO -> Atherosclerosis

Koeth et al. (2013). Nat Med. 19(5): 576–585.

Atherosclerosis

Rath et al. (2017). Microbiome. 5:54.

Many bacterial genes with the same function

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 2014. 5(1):5-10.

Archaeobiotic X Atherosclerosis

Brugere et al. Gut Microbes 2014. 5(1):5-10.

Thanks!

c.hoffmann@usp.br

Funding

Charis Tsevis. 2013. https://www.flickr.com/photos/tsevis/