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音频文本：
Interviewer: Benjamin Thompson
Listeners, we often talk about the gut microbiota on the podcast, and this is of course the community of microbes that live in our intestines. The formation of the early gut microbiota, which happens after birth and during early infancy, is believed to be a particularly important window of time that could have long-lasting effects on our immune system. However, while a lot of research has looked at the effects that colonising microbes have on the developing immune system, there has been less research on the other side of the coin - namely, how the immune system affects the microbes. Well, in a Nature paper this week, Mathias Hornef has been redressing that balance. He is looking at how the immune system shapes which bacteria become part of the microbiota in mice. This shaping is an important process, as he explains.
Interviewee: Mathias Hornef
The current kind of information that we have indicates that after birth, any type of bacteria can colonise the gut, and it is hard to imagine that this would be beneficial for the host. So, we would think that the host organism actually prefers a certain type of bacteria to colonise, and that the host should try to regulate this process and limit maybe colonisation by some and favour colonisation by other bacteria that are more beneficial.
Interviewer: Benjamin Thompson
To work out how this might be happening, Mathias and his colleagues focused on a particular immune molecule that’s known to impact the gut microbiota in mice – it’s called TLR5. Now, broadly speaking, TLR5’s job is to recognise a protein found on the outside of some bacteria called flagellin. If detected, TLR5 then switches on an immune response to deal with the invading bacteria. During the first two weeks of a mouse’s life, Mathias and his colleagues found high levels of TLR5 in the cells that line the small intestine. Although these levels quickly dropped off, this short window of time made a big difference, as these mice had far fewer flagellated bacteria present in their gut microbiota. Mathias also looked at mice which had been engineered to not have TLR5 in their intestines, and their gut microbiota looked very different, containing a lot more flagellated bacteria. And that’s not all…
Interviewee: Mathias Hornef
This seems to persist for 150 days – that’s what we looked at. And this is much longer than the 30 days TLR5 is actually expressed in the gut epithelium.
Interviewer: Benjamin Thompson
This short-lived mechanism seems to have a long-lasting influence. These results offer a new insight into how the early gut microbiota is shaped.
Interviewee: Mathias Hornef
I think the take-home message is that there does exist a mechanism in the neonate that favours the colonisation of certain bacteria, and disfavours the colonisationof others. And interestingly, this mechanism only exists in the neonate, but the effect actually persists throughout life, at least in mice.
Interviewer: Benjamin Thompson
Knowing how the immune system shapes bacterial colonisation will give researchers a better understanding of what’s going on in early life. This window of opportunity is really important, as Lizzie Mann, a gut microbiome microbiota researcher, who was not part of the study, explains.
Interviewee: Lizzie Mann
I think there’s been a whole load of evidence showing that it’s a really critically important window during development where microbiota interactions shape immune homeostasis and immune function, but also susceptibility to disease later in life. And we know that the microbiota that establishes then plays a really big role on how the immune system develops in the gut, what diseases we get, but the mechanisms are still quite unclear. So, I think what’s great about this paper is it really starts to unravel how that actually happens.
Interviewer: Benjamin Thompson
This work might begin to unravel how the early immune system modifies the gut microbiota, but it’s by no means the end of the conversation – we are just beginning to learn how one affects the other. It’s a fantastically nuanced system, with many environmental and genetic factors at play. Not to mention of course, this current work is in mice, and the mechanisms involved might be completely different in humans. Here’s Mathias again.
Interviewee: Mathias Hornef
I think definitely that it may be different in humans. The interesting thing here is that this type of mechanism does exist, because we previously didn’t know this. So, I’m sure in humans there are also mechanisms that kind of shape the early microbiome, whether they are TLR5 or any other TLR or any other mechanism, I don’t know. But the human has the same kind of problems to deal with.
Interviewer: Benjamin Thompson
That was Mathias Hornef from the RWTH Aachen University in Germany. You also heard from Lizzie Mann from the University of Manchester in the UK. You can read Mathias’ paper over at nature.com/nature.ⓝ
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