Understanding the
Human Microbiome
Larry J. Forney, Ph.D.University of Idaho
Tuesday, August 26, 2008
The microbial communities of humans are characteristic and complex mixtures of microorganisms that have co-evolved with their human hosts. The species that make up these communities vary between hosts as a result of restricted migration of microorganisms between hosts and strong ecological interactions within hosts, as well as host variability in terms of diet, genotype and colonization history. The shared evolutionary fate of humans and their symbiotic bacteria has selected for mutualistic interactions that are essential for human health, and ecological or genetic changes that uncouple this shared fate can result in disease. In this way, looking to ecological and evolutionary principles might provide new strategies for restoring and maintaining human health.
From: An ecological and evolutionary perspective on human–microbe mutualism and disease. (2007) Les Dethlefsen, Margaret McFall-Ngai & David A. Relman. Nature 449, 811-818
Tuesday, August 26, 2008
From: An ecological and evolutionary perspective on human–microbe mutualism and disease. (2007) Les Dethlefsen, Margaret McFall-Ngai & David A. Relman. Nature 449, 811-818
Tuesday, August 26, 2008
High numbers, high diversity, low recovery
Variation among individuals
Spatial variation within individuals
Three big problems faced in efforts to understand
these ecosystems
Tuesday, August 26, 2008
The Importance of Understanding Normal Vaginal Communities
The bacterial communities normally found in the vagina represent the first line of defense against infectious
diseases affecting the female reproductive tract.
Common wisdom:
‣ pH of the vagina is low (~4.5).
‣ Restricts growth of nonindigenous organisms, including pathogens.
‣ Lactobacillus spp. are characteristic of vaginal flora in normal healthy women.
study design
Tuesday, August 26, 2008
‣ Are there different kinds of communities in different healthy women?
‣ If so, are the communities functionally equivalent?
‣ Are there differences among racial groups?
‣ Do these differences have important consequences for women’s health?
ObjectiveDetermine composition and structure of microbial
communities in the human vagina.
MotivationCan not discriminate between normal and abnormal conditions
until normal conditions have been accurately defined.
Research questions
study design
Tuesday, August 26, 2008
Tiered Approach‣ Community profiles based on terminal
restriction fragment length polymorphisms of 16S rRNA genes ➙ Different kinds of communities
‣ Phylogenetic analysis of cloned 16S rRNA gene sequences ➙ Species composition of communities
Screen large number of samples
⬇Identify
representative samples
⬇In-depth analysis of selected samples
Statistics analyses that account for metadata.
study design
Will the need for a tiered approach be obviated by the continued development and ‘democratization’
of sequencing technologies?
Probably.
Tuesday, August 26, 2008
Secondary Structure: small subunit ribosomal RNA
Escherichia coli
Nov 1999
(J01695)
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5’
3’
I
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III
Symbols Used In This Diagram:
G A
- Canonical base pair (A-U, G-C)
- G-A base pair- G-U base pair
G C
G U
U U - Non-canonical base pair
Citation and related information available at http://www.rna.ccbb.utexas.edu
Every 10th nucleotide is marked with a tick mark,and every 50th nucleotide is numbered.Tertiary interactions with strong comparative data are connected by solid lines.
1. Bacteria 2. Proteobacteria 3. gamma subdivision4. Enterobacteriaceae and related symbionts5. Enterobacteriaceae 6. Escherichia
analytical methods
Tuesday, August 26, 2008
T-RFLP[Terminal restriction fragment length polymorphism analysis of 16S rRNA genes]
Fragment Size (bp)
Frag
men
t Abu
ndan
ce
(flu
ores
ence
)
5’ 3’
E EE
E EE
Tuesday, August 26, 2008
Coolen et al. Microbiology 71: 8729-8737, 2005
T-RFLP Profiles1 primer pair, 1 restriction enzymeGeneScan® 3.1 untitled Display-1 Page 1 of 1
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Tue, Sep 05, 2000 - 1 - Not For Use In Diagnostic Procedures
Woman 2
Woman 3
Woman 4
Woman 1
Woman 5
Qua
ntity
(fl
uore
scen
ce)
Fragment size (bp)
Tuesday, August 26, 2008
High Resolution T-RFLP Profiles2 primer pairs, 2 restriction enzymes
Qua
ntity
(fl
uore
scen
ce)
Fragment size (bp)
Tuesday, August 26, 2008
Still another miracle happens
PCR
Another miracle happens
A miracle happens
Vaginal swabs
Extract bacterial DNA
Community 16S rRNA genes
Community fingerprints T-RFLP of 16S rRNA genes
Number of different kinds of communities
Libraries of 16 S rRNA genes
Sequence cloned genes
Composition of communitiesAnalytical Procedure
Reference: Abdo et al., Environmental Microbiology 8: 929-938, 2006; http://www.ibest.uidaho.edu/tools/hitsa/index.php
Tuesday, August 26, 2008
Groups
Ave. Distance B
etween C
lusters
Zhou et al. ISME J 1: 121-133, 2007
results
Tuesday, August 26, 2008
Twelve groups with ≥ 2 women
Eight “Supergroups”
These supergroups account for all that occur in the general populace at a frequency of >0.05 (p=.99)
There is a long ‘tail’, i.e., many women will have communities that
differ from those shown here.
Table1. Species composition of vaginal communities in healthy Caucasian and Black women.
Supergroupb (% clones)
I II III IV V VI VII VIII Phylotypea G1 S4 S7 G2 G5 G3 G10 G12 G4 G6 G7 G9 G11 Lactobacillus iners 86.1 93.3 96.8 0.6 0.0 7.0 2.4 0.0 52.1 1.0 0.0 3.6 0.0 Lactobacillus crispatus 0.6 1.1 3.2 93.3 86.8 0.2 0.0 0.0 23.8 19.0 50.5 0.0 0.0 Lactobacillus jensenii 0.5 0.0 0.0 1.5 10.0 0.0 0.0 0.0 6.3 0.3 49.5 0.0 0.0 Lactobacillus gasseri 0.5 0.0 0.0 0.0 2.4 6.4 0.0 0.0 4.5 77.4 0.0 0.0 0.0 Lactobacillus vaginas 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.4 0.0 0.0 0.0 Lactobacillus coleohominis 0.2 0.0 0.0 0.0 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Lactobacillus salivarius c 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Actinobaculum sp. c 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Aerococcus sp. 1.1 2.3 0.0 0.0 0.0 0.5 2.4 1.1 0.3 0.0 0.0 0.0 0.0 Anaerobranca sp. 0.1 0.0 0.0 0.0 0.0 0.1 9.8 0.0 0.0 0.0 0.0 0.0 0.0 Anaerococcus sp. c 0.2 0.0 0.0 0.0 0.0 3.9 0.0 1.1 0.0 0.0 0.0 0.0 0.0 Atopobium vaginae 1.5 0.0 0.0 0.0 0.0 16.9 4.9 27.8 0.0 0.3 0.0 0.0 3.4 Clostridium sp. 0.2 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Dialister sp. 0.0 0.0 0.0 0.0 0.0 2.3 4.9 3.3 0.0 0.0 0.0 0.0 0.0 Eggerthella hongkongensis 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Enterococcus faecalis 0.0 0.0 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Finegoldia magna 0.0 1.1 0.0 0.0 0.0 0.0 0.0 2.2 0.0 0.0 0.0 0.0 0.0 Gardnerella vaginalis 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.4 0.0 0.0 0.0 Gemella palasticanis 0.3 0.0 0.0 0.0 0.0 1.1 0.0 7.8 0.0 0.0 0.0 4.8 0.0 Lachnospiraceae sp. 0.4 0.0 0.0 0.0 0.0 2.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Leptotrichia sp. 0.0 0.0 0.0 0.0 0.0 2.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Megasphaera sp. 1.1 2.2 0.0 0.0 0.0 5.5 9.8 12.2 0.0 0.0 0.0 0.0 10.3 Micromonas sp. 0.4 0.0 0.0 0.0 0.0 7.0 0.0 6.7 0.0 0.0 0.0 0.0 4.5 Mobiluncus mulieris c 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 2.3 Mycoplasma sp. c 0.0 0.0 0.0 0.0 0.0 0.0 2.4 0.0 0.0 0.0 0.0 0.0 0.0 Peptococcus niger c 0.0 0.0 0.0 0.0 0.0 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Peptoniphilus sp. 0.3 0.0 0.0 0.0 0.0 1.5 9.8 1.1 0.0 0.0 0.0 0.0 3.4 Peptostreptococcus sp. c 0.0 0.0 0.0 0.0 0.0 5.0 29.3 0.0 0.0 0.0 0.0 0.0 0.0 Prevotella sp. 0.0 0.0 0.0 0.0 0.0 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Pseudomonas sp. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.4 0.0 0.0 0.0 0.0 Staphylococcus sp. 0.0 0.0 0.0 2.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Streptococcus sp. 0.8 0.0 0.0 1.8 0.0 0.0 0.0 0.0 11.8 0.3 0.0 91.6 0.0 Veillonella sp. 0.2 0.0 0.0 0.0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Novel cladec, d 3.1 0.0 0.0 0.0 0.0 1.9 0.0 0.0 0.0 0.0 0.0 0.0 72.4 Miscellaneous novel phylotypese 2.3 0.0 0.0 0.1 0.6 32.5 24.3 36.7 1.0 0.8 0.0 0.0 3.7 Total number of women (per group) 50 1 1 24 9 20 2 2 10 8 4 2 2 Number of Caucasian women 24 1 1 16 7 5 0 0 9 5 4 1 0 Number of Black women 26 0 0 8 2 15 2 2 1 3 0 1 2 Number of women (per supergroup) 52 33 24 10 8 4 2 2
a The classification of clones was done by comparing their 16S rRNA gene sequences to those of known organisms. The genus and species names were used if the sequence similarity to a type species was >97%; the genus name only was used if the sequence similarity was <97% but >90%; and a clone was designated as novel if the sequence similarity to known organisms was <90%.
b Mean relative abundances of populations in clone libraries analyzed. “G” indicates cluster of > 1 sample, “S” designates a single sample (‘singleton’).
c Not found in Caucasian women. d Single clade of the family Lachnospiraceae that was unrelated to any named bacterium, but closely related (>97% 16S rRNA gene sequence
similarity) to an uncultured bacterium (GenBank AY471619). See Fig. 3b. e Includes various phylotypes within the phylum Firmicutes, including those shown in Fig. 3b.
Zhou et al. ISME J 1: 121-133, 2007
Tuesday, August 26, 2008
SUMMARY: Species composition of vaginal communities in healthy Caucasian and Black women.
Supergroupb (% clones)
I II III IV V VI VII VIII
Phylotypea G1 S4 S7 G2 G5 G3 G10 G12 G4 G6 G7 G9 G11
Lactobacillus iners 86.1 93.3 96.8 0.6 0.0 7.0 2.4 0.0 52.1 1.0 0.0 3.6 0.0
Lactobacillus crispatus 0.6 1.1 3.2 93.3 86.8 0.2 0.0 0.0 23.8 19.0 50.5 0.0 0.0
Lactobacillus jensenii 0.5 0.0 0.0 1.5 10.0 0.0 0.0 0.0 6.3 0.3 49.5 0.0 0.0
Lactobacillus gasseri 0.5 0.0 0.0 0.0 2.4 6.4 0.0 0.0 4.5 77.4 0.0 0.0 0.0
Lactobacillus vaginas 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.4 0.0 0.0 0.0
Aerococcus sp. 1.1 2.3 0.0 0.0 0.0 0.5 2.4 1.1 0.3 0.0 0.0 0.0 0.0
Anaerobranca sp. 0.1 0.0 0.0 0.0 0.0 0.1 9.8 0.0 0.0 0.0 0.0 0.0 0.0
Anaerococcus sp. c 0.2 0.0 0.0 0.0 0.0 3.9 0.0 1.1 0.0 0.0 0.0 0.0 0.0
Atopobium vaginae 1.5 0.0 0.0 0.0 0.0 16.9 4.9 27.8 0.0 0.3 0.0 0.0 3.4
Dialister sp. 0.0 0.0 0.0 0.0 0.0 2.3 4.9 3.3 0.0 0.0 0.0 0.0 0.0
Gemella palasticanis 0.3 0.0 0.0 0.0 0.0 1.1 0.0 7.8 0.0 0.0 0.0 4.8 0.0
Lachnospiraceae sp. 0.4 0.0 0.0 0.0 0.0 2.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0
Leptotrichia sp. 0.0 0.0 0.0 0.0 0.0 2.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0
Megasphaera sp. 1.1 2.2 0.0 0.0 0.0 5.5 9.8 12.2 0.0 0.0 0.0 0.0 10.3
Micromonas sp. 0.4 0.0 0.0 0.0 0.0 7.0 0.0 6.7 0.0 0.0 0.0 0.0 4.5
Peptoniphilus sp. 0.3 0.0 0.0 0.0 0.0 1.5 9.8 1.1 0.0 0.0 0.0 0.0 3.4
Peptostreptococcus sp. c 0.0 0.0 0.0 0.0 0.0 5.0 29.3 0.0 0.0 0.0 0.0 0.0 0.0
Streptococcus sp. 0.8 0.0 0.0 1.8 0.0 0.0 0.0 0.0 11.8 0.3 0.0 91.6 0.0
Novel cladec, d
3.1 0.0 0.0 0.0 0.0 1.9 0.0 0.0 0.0 0.0 0.0 0.0 72.4
Miscellaneous novel phylotypese 2.3 0.0 0.0 0.1 0.6 32.5 24.3 36.7 1.0 0.8 0.0 0.0 3.7
Total number of women (per group) 50 1 1 24 9 20 2 2 10 8 4 2 2
Number of Caucasian women 24 1 1 16 7 5 0 0 9 5 4 1 0
Number of Black women 26 0 0 8 2 15 2 2 1 3 0 1 2
Number of women (per supergroup) 52 33 24 10 8 4 2 2
Zhou et al. ISME J advance online publication, May 10, 2007; doi:10.1038/ismej.2007.12
Tuesday, August 26, 2008
Table1. Species composition of vaginal communities in healthy Caucasian and Black women.
Supergroupb (% clones)
I II III IV V VI VII VIII Phylotypea G1 S4 S7 G2 G5 G3 G10 G12 G4 G6 G7 G9 G11 Lactobacillus iners 86.1 93.3 96.8 0.6 0.0 7.0 2.4 0.0 52.1 1.0 0.0 3.6 0.0 Lactobacillus crispatus 0.6 1.1 3.2 93.3 86.8 0.2 0.0 0.0 23.8 19.0 50.5 0.0 0.0 Lactobacillus jensenii 0.5 0.0 0.0 1.5 10.0 0.0 0.0 0.0 6.3 0.3 49.5 0.0 0.0 Lactobacillus gasseri 0.5 0.0 0.0 0.0 2.4 6.4 0.0 0.0 4.5 77.4 0.0 0.0 0.0 Lactobacillus vaginas 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.4 0.0 0.0 0.0 Lactobacillus coleohominis 0.2 0.0 0.0 0.0 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Lactobacillus salivarius c 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Actinobaculum sp. c 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Aerococcus sp. 1.1 2.3 0.0 0.0 0.0 0.5 2.4 1.1 0.3 0.0 0.0 0.0 0.0 Anaerobranca sp. 0.1 0.0 0.0 0.0 0.0 0.1 9.8 0.0 0.0 0.0 0.0 0.0 0.0 Anaerococcus sp. c 0.2 0.0 0.0 0.0 0.0 3.9 0.0 1.1 0.0 0.0 0.0 0.0 0.0 Atopobium vaginae 1.5 0.0 0.0 0.0 0.0 16.9 4.9 27.8 0.0 0.3 0.0 0.0 3.4 Clostridium sp. 0.2 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Dialister sp. 0.0 0.0 0.0 0.0 0.0 2.3 4.9 3.3 0.0 0.0 0.0 0.0 0.0 Eggerthella hongkongensis 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Enterococcus faecalis 0.0 0.0 0.0 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Finegoldia magna 0.0 1.1 0.0 0.0 0.0 0.0 0.0 2.2 0.0 0.0 0.0 0.0 0.0 Gardnerella vaginalis 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.0 0.4 0.0 0.0 0.0 Gemella palasticanis 0.3 0.0 0.0 0.0 0.0 1.1 0.0 7.8 0.0 0.0 0.0 4.8 0.0 Lachnospiraceae sp. 0.4 0.0 0.0 0.0 0.0 2.8 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Leptotrichia sp. 0.0 0.0 0.0 0.0 0.0 2.9 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Megasphaera sp. 1.1 2.2 0.0 0.0 0.0 5.5 9.8 12.2 0.0 0.0 0.0 0.0 10.3 Micromonas sp. 0.4 0.0 0.0 0.0 0.0 7.0 0.0 6.7 0.0 0.0 0.0 0.0 4.5 Mobiluncus mulieris c 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 2.3 Mycoplasma sp. c 0.0 0.0 0.0 0.0 0.0 0.0 2.4 0.0 0.0 0.0 0.0 0.0 0.0 Peptococcus niger c 0.0 0.0 0.0 0.0 0.0 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Peptoniphilus sp. 0.3 0.0 0.0 0.0 0.0 1.5 9.8 1.1 0.0 0.0 0.0 0.0 3.4 Peptostreptococcus sp. c 0.0 0.0 0.0 0.0 0.0 5.0 29.3 0.0 0.0 0.0 0.0 0.0 0.0 Prevotella sp. 0.0 0.0 0.0 0.0 0.0 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Pseudomonas sp. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.4 0.0 0.0 0.0 0.0 Staphylococcus sp. 0.0 0.0 0.0 2.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Streptococcus sp. 0.8 0.0 0.0 1.8 0.0 0.0 0.0 0.0 11.8 0.3 0.0 91.6 0.0 Veillonella sp. 0.2 0.0 0.0 0.0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Novel cladec, d 3.1 0.0 0.0 0.0 0.0 1.9 0.0 0.0 0.0 0.0 0.0 0.0 72.4 Miscellaneous novel phylotypese 2.3 0.0 0.0 0.1 0.6 32.5 24.3 36.7 1.0 0.8 0.0 0.0 3.7 Total number of women (per group) 50 1 1 24 9 20 2 2 10 8 4 2 2 Number of Caucasian women 24 1 1 16 7 5 0 0 9 5 4 1 0 Number of Black women 26 0 0 8 2 15 2 2 1 3 0 1 2 Number of women (per supergroup) 52 33 24 10 8 4 2 2
a The classification of clones was done by comparing their 16S rRNA gene sequences to those of known organisms. The genus and species names were used if the sequence similarity to a type species was >97%; the genus name only was used if the sequence similarity was <97% but >90%; and a clone was designated as novel if the sequence similarity to known organisms was <90%.
b Mean relative abundances of populations in clone libraries analyzed. “G” indicates cluster of > 1 sample, “S” designates a single sample (‘singleton’).
c Not found in Caucasian women. d Single clade of the family Lachnospiraceae that was unrelated to any named bacterium, but closely related (>97% 16S rRNA gene sequence
similarity) to an uncultured bacterium (GenBank AY471619). See Fig. 3b. e Includes various phylotypes within the phylum Firmicutes, including those shown in Fig. 3b.
95/144 women
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0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
I II IV III V VI VII VIII
Supergroup
FrequencyBlack Caucasian
Zhou et al. ISME J advance online publication, May 10, 2007; doi:10.1038/ismej.2007.12
results
Tuesday, August 26, 2008
‣ Ecological function of communities – lactic acid production – is conserved.
‣ Not all vaginal communities were dominated by species of Lactobacillus.
‣ Suggests that hosts exert selective pressures that shape the composition of communities.
Observations
background
(1) There were (only) eight common kinds of vaginal communities with fundamentally different species composition.
(2) Rank-abundance of communities differs among racial groups
Tuesday, August 26, 2008
community ecology
Tuesday, August 26, 2008
An ecosystem
Community
Host
Environment
community ecology
Tuesday, August 26, 2008
Effect of Disturbances on Vaginal Communities
Normal[Dynamic equilibrium]
DisturbedEcosystem
Frequency or Duration
Inte
nsity
Disturbances to the vaginal environment are often imposed by human actions:
- douching
- intercourse
- birth control methods
But also include:
- menstruation
- menopause
- parturition
➙
community ecology
Tuesday, August 26, 2008
So what factors are key to ecosystem stability?
‣ The strong linkage between high numbers of lactic acid bacteria and a ‘healthy’ vaginal microbial community is consistent with Walker’s Driver-Passenger model of community structure and function (Walker, 1995).
‣ Under this model, species of lactic acid bacteria would be considered ‘drivers’ that strongly influence the function or structure of the ecosystem by producing lactic acid and maintaining a low pH.
‣ The environment thus created would be a strong determinant of community species composition and activity because they would all have to flourish or at least tolerate an environmental pH of 4.0-4.5.
‣ The non-lactic acid bacteria would be considered ‘passengers’ that are typically present at lower numerical abundance, have little influence on the ecology of the system, and can be lost from the community or change over time without markedly affecting community function.
community ecologyspeculation
Lactic acid bacteria (LAB) Includes, but are not limited to, species of Lactobacillus
Tuesday, August 26, 2008
Resilience
Resilience is the amount of disturbance that an ecosystem can withstand without changing its self-organizing processes.
‣ Not all disturbances have equal intensity, occur at the same frequency, or endure for the same length of time. Therefore, not all disturbances have the same consequences.
‣ Communities with fundamental differences in species composition and structure will differ in resilience.
community ecology
http://www.affordablehousinginstitute.org/blogs/us/Train_wreck_2_vertical_small.jpg
Ecological Disequilibrium
Disturbed communities are more readily invaded by “weedy” species (opportunistic pathogens).
Tuesday, August 26, 2008
0 20 40 60 80 100 120 140
1015
2025
3035
40
Time
Com
mun
ity S
truct
ure
Mean CommunityStructure
BV
Com
mun
ity S
truc
ture
Time
Bacterial vaginosis
0 20 40 60 80 100 120 140
1015
2025
3035
40
TimeCo
mm
unity
Stru
ctur
e
Mean CommunityStructure
BV
TimeC
omm
unity
Str
uctu
re
Bacterial vaginosis
speculation
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speculation
0 20 40 60 80 100 120 140
1015
2025
3035
40
Time
Com
mun
ity S
truct
ure
Mean CommunityStructure
BV
Disturbance
Time
Com
mun
ity S
truc
ture Bacterial vaginosis
Disturbance
Tuesday, August 26, 2008
community ecology
‣Disturbances provide opportunities for invasive species to become established in a community.
‣The disturbed state itself could be a disease.
‣Not all diseases are caused by a single etiological agent.
Host
Environment Community
DISTURBED
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No role proposed for normal microbiota
sickhost
isolatesuspected
causitive agent
infect healthy host
new host becomes sick
Germ Theory of Infectious Disease
Gause's Law of Competitive Exclusion A theory that states that two species competing
for the same resources cannot stably coexist
community ecology
Tuesday, August 26, 2008
proteins
polysaccharides,monosaccharides,
urea
Na+, K+, Cl-
Host
MicrobialCommunity
community ecology
All resources used by vaginal microbial
populations are derived from the host
Quantity and composition of resources probably
differ among hosts
Competition for resources is probably severe
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Community
Host
Environment
community ecology
Mutualism: both parties benefitCommensalism
Tuesday, August 26, 2008
Conclusions
Forney Lab- Xia Zhou, MD- Jacob Pierson- Maria Schneider
Collaborators:
University of Idaho- Zaid Abdo, PhD- James Foster, PhD- Steve Krone, PhD- Chris Williams, PhD
University of Maryland- Jacques Ravel, PhD
Procter and Gamble- Catherine Davis, PhD
Funding:NIHP&G
Tuesday, August 26, 2008
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