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!