Challenges in the measurement of the microbiome

Emma Allen-Vercoe

Model microbiomes

• Important to study a microbial ecosystem as an ecosystem– It is more than the sum of its parts

• For the gut (and oral) communities, continuous culture (chemostat) systems have been developed– Have plans for a vaginal chemostat

Chemostats

Pros• Ethically acceptable• Can run for several weeks or

more• Cheaper than animal

studies • Controllable • Metabolites not absorbed• Sample all you need, when

you want to

Cons• No host side to the

equation • Some components of the

ecosystems may be lost• Liquid phase necessary

Our “Roboguts”

•Seeded with fresh feces and set to model the distal gut ecosystem•Host-free system•Can be used to support growth of fastidious gut anaerobes

Simplified (defined) communities

• Human gut ecosystems display functional redundancy– Can we therefore create simplified, defined

communities?• Working on this…

– Defined ecosystems are highly reproducible (fecal ecosystems are not (between donations))

– Currently using iPath to indicate functional redundancy in order to rationally design ecosystems

– Can test them for e.g. function and stability in chemostats

Mathematical modeling of ecosystems

• Collaborations with theoretical biologists– Can we create model microbial ecosystems in silico?

• Very early days – only 2 or 3 strain ecosystems can be modeled at one time (processing constraints? Programming constraints?)

• Need more communication between mathematics and biology

• Start process early for maximum benefit!

A shout out for metabolomics

• It’s not what’s there, it’s what they are doing that’s important!– Profiling small molecules is like eavesdropping on

microbial conversations• Powerful when combined with in vitro modeling

– Best methods? MS? NMR? Both?• Need better predictive tools to get from

metagenomes to small molecules– What’s the pathway?

“Liquid gold”

Allows us to eavesdrop on microbial conversations!