bis2c: lecture 13: the human microbiome

Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016

Lecture 13: The Human Microbiome

BIS 002C Biodiversity & the Tree of Life

Spring 2016

Prof. Jonathan Eisen

Where we are going and where we have been

• Previous Lecture: !12: Novelty

• Current Lecture: !13: The Human Microbiome

• Next Lecture: !14: Big Organisms

Key Concepts and Outline

• Humans are swarming with microbes

• Microbiomes are Complex Ecosystems

• Enormous Variation within & between People

• Variation is Associated with Various Health States and Phenotypes

• Possible Causes of the Variation Have Been Identified

• It May Be Possible to Alter / Restore the Microbiome

Classes of symbiosis

Organism

Class of symbiosis A B

Mutualism + +

Commensalism + 0

Parasitism + -

Organism

Mutualism + +

Commensalism + 0

Parasitism + -

The Human Microbiome

Summer 2012 Workshop in Biology and Multimedia for High School Teachers

Microbes are all over us

8http://commons.wikimedia.org/wiki/File:Man_shadow_-_upper.png

Thousands of different species on the skin alone

Some thrive on dry patches of the elbow, others

thrive in moist environment of armpit

There are millions of microbes

per square inch on your body

It is estimated that there are more microbes

in your intestine than there are human cells

in your body!

Who Are We?

microBIOME or microbiOME

• microbi-OME !collection of genomes of microbes from a

community (emphasis on OME)

• micro-BIOME !a community of microbes (emphasis on

BIOME)

• see http://tinyurl.com/definemicrobiome

Clicker

Which of the following lineages contain microbes?

A: Bacteria

B: Archaea

C: Eukaryotes D: All of the above

E: None of the above

Clicker

Which of the following lineages contain microbes?

A: Bacteria

B: Archaea

C: Eukaryotes D: All of the above

E: None of the above

The Rise of the Microbiome

00 01 02 03 04 05 06 07 08 09 10 11 12

Pubmed “Microbiome” Hits

Organism

Mutualism + +

Commensalism + 0

Parasitism + -

Why All The Attention for Commensalism?

Organism

Mutualism + +

Commensalism + 0

Parasitism + -

Is this Mutualism?

Organism

Mutualism + +

Commensalism + 0

Parasitism + -

Is this Parasitism?

Organism

Mutualism + +

Commensalism + 0

Parasitism + -

Some of Each

Why Now? Studies Like This …

Turnbaugh et al Nature. 2006 444(7122):1027-31.

Microbiome Involved in Many Functions

• Digestion

• Vitamin Production

• Protection from parasites / pathogens

• Metabolic rate

• Immune regulation

• Odor

• Behavior

Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016 22

Why Now II: DNA Sequencing Advances

Great Plate Count Anomaly

Culturing Observation

CountCount

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=rLu5sL207WlE1M&tbnid=CRLQYP7d9d_TcM:&ved=0CAUQjRw&url=http

%3A%2F%2Fwww.biol.unt.edu%2F~jajohnson

%2FDNA_sequencing_process&ei=hFu7U_TyCtOqsQSu9YGwBg&psig=AFQjCNG-8EB

dEljE7-yHFG2KPuBZt8kIPw&ust=14048739512114

Archaea

Woese Classification of Cultured Taxa by rRNA

rRNA rRNArRNA

ACUGC ACCUAU CGUUCG

ACUCC AGCUAU CGAUCG

ACCCC AGCUCU CGCUCG

Taxa Characters S ACUGCACCUAUCGUUCG R ACUCCACCUAUCGUUCG E ACUCCAGCUAUCGAUCG F ACUCCAGGUAUCGAUCG C ACCCCAGCUCUCGCUCG W ACCCCAGCUCUGGCUCG

EukaryotesBacteria

CarlWoese

rRNA Taxa Characters B1 ACTGCACCTATCGTTCG B2 ACTCCACCTATCGTTCG E1 ACTCCAGCTATCGATCG E2 ACTCCAGGTATCGATCG A1 ACCCCAGCTCTCGCTCG A2 ACCCCAGCTCTGGCTCG New ACCCCAGCTCTGCCTCG

EukaryotesBacteria Archaea

Culture Independent Studies

ACTGC ACCTAT CGTTCG

Many sequences from one sample all point to the same branch on the tree

NormPace

Taxa Characters B1 ACTGCACCTATCGTTCG B2 ACTCCACCTATCGTTCG E1 ACTCCAGCTATCGATCG E2 ACTCCAGGTATCGATCG A1 ACCCCAGCTCTCGCTCG A2 ACCCCAGCTCTGGCTCG New1 ACCCCAGCTCTGCCTCG New2 AGGGGAGCTCTGCCTCG New3 ACTCCAGCTATCGATCG New4 ACTGCACCTATCGTTCG

EukaryotesBacteria Archaea

ACTGC ACCTAT CGTTCG

ACTCC AGCTAT CGATCG

ACCCC AGCTCT CGCTCG

AGGGG AGCTCT CGCTCG

ACTGC ACCTAT CGTTCG

Even with more taxa it still works

Culture Independent Studies

Metagenomics Has Many Other Purposes

metagenomics

ACUGC ACCUAU CGUUCG

ACUCC AGCUAU CGAUCG

ACCCC AGCUCU CGCUCG

Taxa Characters S ACUGCACCUAUCGUUCG R ACUCCACCUAUCGUUCG E ACUCCAGCUAUCGAUCG F ACUCCAGGUAUCGAUCG C ACCCCAGCUCUCGCUCG W ACCCCAGCUCUGGCUCG

inputs of fixed carbon or nitrogen from external sources. As withLeptospirillum group I, both Leptospirillum group II and III have thegenes needed to fix carbon by means of the Calvin–Benson–Bassham cycle (using type II ribulose 1,5-bisphosphate carboxy-lase–oxygenase). All genomes recovered from the AMD system

contain formate hydrogenlyase complexes. These, in combinationwith carbon monoxide dehydrogenase, may be used for carbonfixation via the reductive acetyl coenzyme A (acetyl-CoA) pathwayby some, or all, organisms. Given the large number of ABC-typesugar and amino acid transporters encoded in the Ferroplasma type

Figure 4 Cell metabolic cartoons constructed from the annotation of 2,180 ORFs

identified in the Leptospirillum group II genome (63% with putative assigned function) and

1,931 ORFs in the Ferroplasma type II genome (58% with assigned function). The cell

cartoons are shown within a biofilm that is attached to the surface of an acid mine

drainage stream (viewed in cross-section). Tight coupling between ferrous iron oxidation,

pyrite dissolution and acid generation is indicated. Rubisco, ribulose 1,5-bisphosphate

carboxylase–oxygenase. THF, tetrahydrofolate.

articles

Clicker

How could you tell if one of the rRNA genes you sequence came from a chloroplast?

A: It should group in rRNA trees with plant nuclear rRNA genes.

B: It should group in rRNA trees with proteobacteria.

C: It should group in rRNA trees with cyanobacteria.

D. It should group in rRNA trees with TACK

E: You can’t tell.29

Clicker

How could you tell if one of the rRNA genes you sequence came from a chloroplast?

A: It should group in rRNA trees with plant nuclear rRNA genes.

B: It should group in rRNA trees with proteobacteria.

C: It should group in rRNA trees with cyanobacteria.

D. It should group in rRNA trees with TACK

E: You can’t tell.30

How could you tell if one of the rRNA genes you sequence came from a mitochondrion?

How could you tell if one of the rRNA genes you sequence came from a fungus?

The Human Microbiome

Microbiomes as Ecosystems

Variation Between Countries: Gut

The ISME Journal (2013) 7, 85–95; doi:10.1038/ismej.2012.81MJ Blaser et al. ISMEJ 2012 US Amerindian

Actinobacteria (Propionibacteria)

Firmicutes (Staphylococcus)

e Actinobacteria dominates in the US

Boulder NY Platanillal A Platanillal B

Proteobacteria

Variation Between Countries: Gut

The ISME Journal (2013) 7, 85–95; doi:10.1038/ismej.2012.81MJ Blaser et al. ISMEJ 2012 US Amerindian

Actinobacteria (Propionibacteria)

Firmicutes (Staphylococcus)

e Actinobacteria dominates in the US

Boulder NY Platanillal A Platanillal B

Proteobacteria

Variability Across People

42Huttenhower et al. 2012.

Variability is Correlated to Many Health States

• Microbial community different in many disease states compared to healthy individuals

• Unclear if this is cause or effect in most cases

!45Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79

!46Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79

Age Diet Location

Many disease states

ExposurePregnant?

Breast fed? Obese

Microbiome Involved in Many Functions

• Digestion

• Vitamin Production

• Protection from parasites / pathogens

• Metabolic rate

• Immune regulation

• Odor

• Behavior

Infant Microbiome, Birth, and Milk

David Mills

Other Sources

Disturbing the Microbiome

Antibiotics

Diet Changes

Hygiene Hypothesis

C-sections

C-Sections Alter “Normal” Colonization

Maria Gloria Dominguez-Bello

Diet Changes Alter Microbiome

Switch to solid foods

Response to Antibiotics

by L. iners during menses, which then reverted to a communitydominated by L. crispatus at the end of menses. Similarly, in subject24 (Fig. 2A), a community dominated by L. crispatus is replaced by acommunity dominated by Streptococcus during menses. Communitiesof class LI (14 women, fig. S5) were typically dominated by L. iners,but varied widely in terms of species composition and stability. This isillustrated by the communities of subjects 14, 15, 16, 18, and 19 thatappeared to be comparatively stable over time, whereas others such assubjects 11 and 27 commonly shifted to different community types thatwere more often associated with higher Nugent scores. The underlying

reasons for these differences are unknown but might reflect genomicheterogeneity in the dominating Lactobacillus sp. Heatmaps depictingthe dynamics of vaginal communities in a few selected subjects areshown in Fig. 2; those for all 32 subjects are shown in fig. S5.

Dynamics of the vaginal microbiotaThe rapid and sometimes extensive turnover of human vaginal bacte-rial communities was visualized by mapping temporal changes incommunity composition onto the three-dimensional (3D) communityspace defined previously in a cross-sectional study by Ravel et al. of

Subject 24

L. crispatusL. inersL. jenseniiStaphylococcusL. gasseriCorynebacteriumClostridiumLactobacillales 2L. vaginalisL. otu5

Subject 29

Subject 6

L. inersAtopobiumSneathiaCorynebacteriumGemellaFinegoldiaPrevotellaPeptostreptococcusPeptoniphilusAnaerococcusStreptococcusParvimonasStaphylococcus

Subject 12

Time (weeks)0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

PhylotypesL. crispatus L. iners L. gasseri StaphylococcusL. jensenii Atopobium

Prevotella

Aerococcus

Anaerococcus

Streptococcus

Clostridium

ParvimonasGardnerella Mobiluncus Corynebacterium

Gemella

Finegoldia Peptostreptococcus Peptoniphilus

L. otu5Lactobacillales 2 L. otu3 L. vaginalis L. otu4Sneathia 80 100

Phylotype percentrelative abundance

0 20 40 60

L. crispatusStreptococcusL. reuteriBifidobacteriumAnaerococcusPrevotellaFinegoldiaPeptostreptococcusEscherichiaAlloscardovia

AtopobiumPrevotellaParvimonasPeptoniphilusSneathiaMobiluncusLachnospiraceae 10Ruminococcaceae 3GardnerellaLachnospiraceae 11AerococcusMoryellaPeptococcusLachnospiraceae 2AnaerococcusAllisonellaPeptostreptococcusMegasphaera

Lachnospiraceae 10 Ruminococcaceae 3

Lachnospiraceae 11Moryella PeptococcusLachnospiraceae 2

Allisonella

Megasphaera

L. reuteri Bifidobacterium

Escherichia Alloscardovia

Fig. 2. (A to D) Heatmaps (top) and interpolated bar plots (bottom) ofphylotype relative abundance observed in four selected subjects over 16weeks (heatmap color key is indicated in the lower right corner). Color codes

for each phylotype represented in the interpolated bar plots are shown belowthe figure. See fig. S5 for heatmaps and interpolated bar plots for all subjects.Red dots below the interpolated bar graphs represent menstruation days.

R E S EARCH ART I C L E

www.ScienceTranslationalMedicine.org 2 May 2012 Vol 4 Issue 132 132ra52 4

Hygiene Hypothesis

Susan Lynch

Dogs, Dust, Microbiomes and Asthma

Microbiome Transplant

Restoring the Microbiome: Probiotics and Prebiotics

Intestinal Transplant

59Hartman et al. PNAS 2009

Coprophagia

Transfaunation

Fecal “transplants”

Openbiome

DIY Fecal Transplant

Get Involved

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