META JC 5.3.2013
META JC
5.3.2013
First, some definitions
• Coevolution:
– Happens when two species influence each other’s evolution
– Coevolution is a process of reciprocal evolutionary change in interacting species
• An interaction ≠ coevolution
• Coadaption ≠ coevolution
First, some definitions
• Diffuse coevolution – when a species evolves in response to more than 2 species.
Wigglesworthia glossinidia & Tsetse Fly
W. glossinidia Genome~700,000bp
Squid-Vibrio Symbiosis
V. fischeriE. scolopes
Some questions to keep in mind
• How to show coevolution between host and microbial species vs. host and microbiota?
• How does this paper fit into the hologenometheory of evolution?
• How is ‘evolution of the microbiota’ different from species succession/species composition changes?
• How do these results fit in with the hygiene hypothesis?
Gut microbiome and immune system
T-Helper T-regulatory
Protection from pathogens
Recognition ofSelf
T Cells
CD3+CD4+ CD3+CD8+
T-helper Cells
Th
Th1
Th2
Th17
• Increases activation of macrophages (innate immune system)• Protection against intracellular pathogens (virus and intracellular bacteria)
• Increases B cell activation (adaptive immune system) • Immunity against parasites• Implication in allergies
• Protection against extracellular bacteria• Specific to the gut • Intestinal homeostasis
Cytokines –cell signaling molecules
Biomarkers – distinguish T Cell populations
Figure 2. Consequences of immune system imbalances
Immune system homeostasis involves a regulated balance of inflammatory and anti-
inflammatory cells; however, skewed responses putatively through lack of microbial exposure
or outgrowth of pathogenic species may contribute to imbalances associated with the
development of chronic inflammatory disorders.
Fujimura et al. Page 27
Expert Rev Anti Infect Ther . Author manuscript; available in PMC 2011 February 1.
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Th1 – Increases activation of macrophages (innate immune system)Th2 – Increases B cell activation, immunity against parasites, implication in allergiesTh17 – protection against extracellular bacteria, intestinal homeostasis
Fujimura et al., 2010
Intestinal Morphology
Basic Experimental Design
F0F1F2
F0F1F2
N~70
• 30% of OTUs in human inoculum not present in HMb
• 7% of OTUs in mouse inoculum not present in MMb
• “Lost OTUs” were mostly low abundance Firmicutes.
MMb, not HMb mice exhibit expansion of adaptive and innate immune systems
T Helper Cells Regulatory T Cells
A B
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HMb Mice have Lower Numbers of Memory Cells
N = 7
T Cell Activation
Heat Shock
Th-17
Th-2
Inflammatory Anti-inflammatory
Conclusions
• HMb mice have a reduction in T cell numbersdue to proliferation rate (not cell trafficking)
• HMb mice had more Th2 (implicated in allergies) than Th17 (extracellular pathogen protection)
• Major differences between HMb and MMbwere found in the Firmicutes
• HMb did not do as well when challenged with a pathogen
Some questions to keep in mind
• How to show coevolution between host and microbial species vs. host and microbiota?
• How does this paper fit into the hologenometheory of evolution?
• How is ‘evolution of the microbiota’ different from species succession/species composition changes?
• How do these results fit in with the hygiene hypothesis?