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

1


Where we are going and where we have been

• Previous Lecture: !12: Novelty

• Current Lecture: !13: The Human Microbiome

• Next Lecture: !14: Big Organisms

2


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

4


Classes of symbiosis

Organism

Class of symbiosis A B

Mutualism + +

Commensalism + 0

Parasitism + -

5



Organism


Mutualism + +

Commensalism + 0

Parasitism + -

6


The Human Microbiome

7


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?

9


Who Are We?

10

50


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

11

http://tinyurl.com/definemicrobiome


Clicker

12


Clicker

Which of the following lineages contain microbes?

A: Bacteria

B: Archaea

C: Eukaryotes D: All of the above

E: None of the above

13


Clicker

Which of the following lineages contain microbes?

A: Bacteria

B: Archaea

C: Eukaryotes D: All of the above

E: None of the above

14


The Rise of the Microbiome

15

0

350

700

1050

1400

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

Pubmed “Microbiome” Hits



Organism


Mutualism + +

Commensalism + 0

Parasitism + -

16

Why All The Attention for Commensalism?



Organism


Mutualism + +

Commensalism + 0

Parasitism + -

17

Is this Mutualism?



Organism


Mutualism + +

Commensalism + 0

Parasitism + -

18

Is this Parasitism?



Organism


Mutualism + +

Commensalism + 0

Parasitism + -

19

Some of Each


Why Now? Studies Like This …

20

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

http://www.ncbi.nlm.nih.gov/pubmed/17183312#


Microbiome Involved in Many Functions

• Digestion

• Vitamin Production

• Protection from parasites / pathogens

• Metabolic rate

• Immune regulation

• Odor

• Behavior

21

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

Why Now II: DNA Sequencing Advances


Great Plate Count Anomaly

23

<<<<

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

24

DNAor

RNA


Archaea

Woese Classification of Cultured Taxa by rRNA

24

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

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

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

NormPace


DNA

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

AGGGG AGCTCT CGCTCG

ACTGC ACCTAT CGTTCG

Even with more taxa it still works

Culture Independent Studies


Metagenomics Has Many Other Purposes

27

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

NATURE | doi:10.1038/nature02340 | www.nature.com/nature 5© 2004 Nature Publishing Group


Clicker

28


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?

31


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

32









33


The Human Microbiome

34

Microbiomes as Ecosystems

!35









36


Variation Between Countries: Gut

40

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

Actinobacteria (Propionibacteria)

Firmicutes (Staphylococcus)

Rela

tive

abun

danc

e Actinobacteria dominates in the US

Boulder NY Platanillal A Platanillal B

Proteobacteria


Variation Between Countries: Gut

41

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

Actinobacteria (Propionibacteria)

Firmicutes (Staphylococcus)

Rela

tive

abun

danc

e Actinobacteria dominates in the US

Boulder NY Platanillal A Platanillal B

Proteobacteria


Variability Across People

42Huttenhower et al. 2012.









43


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

44

!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

47









48


Infant Microbiome, Birth, and Milk

49

David Mills


Other Sources

50


Disturbing the Microbiome

51

Antibiotics

Diet Changes

Hygiene Hypothesis

C-sections


C-Sections Alter “Normal” Colonization

52

Maria Gloria Dominguez-Bello


Diet Changes Alter Microbiome

53

Switch to solid foods


Response to Antibiotics

54

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

A B

DC

Subject 24

0

20

40

60

80

100

Phyl

otyp

e re

lativ

e ab

unda

nce

(%)

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

Subject 29

0

20

40

60

80

100

Phyl

otyp

e re

lativ

e ab

unda

nce

(%)

Subject 6

0

20

40

60

80

100

Phyl

otyp

e re

lativ

e ab

unda

nce

(%)

L. inersAtopobiumSneathiaCorynebacteriumGemellaFinegoldiaPrevotellaPeptostreptococcusPeptoniphilusAnaerococcusStreptococcusParvimonasStaphylococcus

Subject 12

0

20

40

60

80

100

Phyl

otyp

e re

lativ

e ab

unda

nce

(%)

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

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

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

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

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Hygiene Hypothesis

55

Susan Lynch

Dogs, Dust, Microbiomes and Asthma









56


Microbiome Transplant

57


Restoring the Microbiome: Probiotics and Prebiotics

58


Intestinal Transplant

59Hartman et al. PNAS 2009


Coprophagia

60


Transfaunation

61


Fecal “transplants”

62


Openbiome

63


DIY Fecal Transplant

64


DIY Fecal Transplant


Get Involved

67

Kitty Microbiome