Microbiome pecking order

Jens Walter explains to Chris Smith how the first types of bacteria to colonize the gut could shape our microbiome as adults...

Jens - One puzzling finding is that each individual has a unique and stable community of gut microbes that is almost as personal as a fingerprint. Studies have not tried to identify what causes this individuality and found that factors such as genetics, diet, environment or lifestyle, also you know health of its theological state only account for around 30 percent of the variation.  And even identical twins actually have different microbiomes. So this suggests that something unknown actually contributes to microbiome individuality. So what we tried in our study now is to determine the factors that contribute to microbiome assembly, and more specifically we tested the hypothesis that differences in the order by which we acquire microbiomes early in life can actually cause variation later in life, and the high level of individual variation that we are observing.

Chris - Why do you think that the order in which we pick up microbes in this way might make a difference at all?

Jens - This is very much based on the ecological theory that colonisation history, or more specifically priority effects, actually influence the outcome of community asembly. Priority effects mean, basically, that an early coloniser will often have an advantage because it is occupying the niche first, and it will also have an impact on the ecosystem by influencing colonisers that come later. Due to this, the order or the timing by which these members in a community arrive will then shape how the community looks in the end and how it functions.

Chris - I suppose it's a bit like if you walked into a room and there was a bunch of empty seats and there was no one sitting in any of them you'd choose any seat to sit in? But if you walked into the same room and there were two or three people sitting down already you might change where you sat and who you spoke to?

Jens - That's an excellent metaphor actually for what we are feeling. In inequality, we are actually referring to this as niche pre-emption. The one who comes first basically sits first.

Chris - Now how did you test this though? Because it's a nice theory, it's a nice idea, but how can you subject that to proper scientific scrutiny to find out if that's really what's going on?

Jens - So we have given this quite a bit of thought. So what we did is we used mice that don't contain any microbes, meaning they were germ free. And these mice were further genetically identical and they were housed exactly under the same condition using airtight plastic bubbles. So what we were basically trying to do is we controlled all of the experimental variables that we could think of. We then associated these mice with either entire microbial communities, or specific bacterial strain cocktails in combination with communities, and we introduced these entities in different succession. We could specifically test if the timing and order of early life colonisation influences how the bacterial community is composed.

Chris - What about the immune system though?  Because I put it to you that when I put a group of bacteria in, they might do something to the immune system which that, in turn, affects the receptivity of the location for whoever comes in next?

Jens - Now that is an excellent question and we are actually giving this quite a bit of thought. We think that early colonisers can somehow interact with the immune system and actually in enthuse tolerogenic immune responses that would then favour this early colonisation. To test for this we actually repeated our experiments in mice that do not have an immune system and therefore cannot actually at least develop immunological tolerance to these early colonisers. And when we did these experiments in these immuno deficient mice we still found a clear evidence for priority effects.

Chris - So what are the implications of this then? Because we've got lots of babies popping out all around the world every day, not all of them are being born via the normal route. Some are being born by say caesarean section. Some are being given big doses of antibiotics when they're born, usually for very good reason, but that could therefore have, based on what you're finding, very profound effects on the future microbiome structure for those individuals.

Jens - We can make two major conclusions here. First, as you said, we get an understanding about you know what actually shapes our microbiome. And since we showed that the early acquisition is important, clinical practices that influenced this early acquisition of the microbiome, such a caesarean sections or antibiotics, formula feeding will actually then influence how the microbiome looked later in life. So appreciation for these ecological events early in life might help us to develop different clinical practices to potentially prevent a barren assemblies of gut microbiomes. The other main thing that we learn is that if we want to modulate the gut microbiome more permenantly we probably have to do this early in life, because early colonisers have a higher success of actually establishing themself in the ecosystem. And not only this, these early colonisation effects might also allow us to specifically out of the entire community establish a more healthy microbiomes or prevent the establishment of microbiomes that might have a detrimental effect in the end.