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

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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?