Constant adaptation

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We tend to think of us humans and animals as static. So once we are made, we do not change. But that is clearly not the case. During a lifetime, there are all sorts of adaptations, ranging from reproduction to nutritional challenges and adjustments to new environments, and that requires very active regulation of what goes on inside us. But even when we’re not changing – or when we’re not aware that we are changing – our body is going to all sorts of extremes to maintain that balance.

For example, we’re very interested in the gastrointestinal tract, in the digestive system. We might think that once we’ve made that organ, that’s it. This is our digestive system. But the lining of the gastrointestinal system is constantly being replenished; it’s constantly facing challenges from the food that we eat and the microbes that live within us. This means that the cells that are there are never the same cells. Within two weeks, they’ve changed; they’re different cells. Yet we need to keep that organ the way it was, or keep it behaving the same way. That is a challenge for the body. Different organs within the body are constantly communicating to achieve that kind of balance – what we call homeostasis.

Challenges to homeostasis

Challenges may come from the inside, from within us, or they may come from the outside. Say, for example, one day we don’t eat, or one day we eat too much. How do we cope with that? How do we maintain the way we are, the way we function in the face of those challenges? Challenges can also come from within us. Think, for example, of what happens to the female body during reproduction. We have an “alien” inside us, and all sorts of things change. We tend to think of reproduction as a period in which there’s a bump growing inside us. But the fact is, many other organs within us change.

It’s been very well documented in many animals that, in fact, many of our organs grow during reproduction. In the particular case of the digestive system, this is believed to allow us to extract more nutrients from what we eat to maximise nutrient extraction for the developing baby. But all this has to be really finely tuned.

It’s all very well when you have a baby inside to make your intestine grow so that it extracts nutrients, but what happens when the baby no longer needs those nutrients? Does the gastrointestinal tract shrink again? We think – and that’s what we’re exploring in our research – that in some cases it may shrink, so you go back to your pre-pregnancy status. But in some other cases, it may not shrink so effectively. And that might be one reason why some of us struggle to lose weight after pregnancy.

How organs communicate

We are learning that organ communication is extremely complex and extremely sophisticated. Historically, we thought it was all about hormones: that organs exchange these so-called little proteins that are made by one organ, and they travel in our bloodstream to a different organ. And that is indeed the case; these hormones are very important. But we’re also learning that there are all sorts of other ways for organs to communicate.

One way that we’ve become really interested in is communication through metabolites. Metabolites molecules within cells, which can also be secreted into circulation. What we’re finding is that the position of organs, the three-dimensional arrangement of organs within us, seems to matter for this kind of communication. So who your neighbouring organ is seems to matter for how you exchange metabolites and how you communicate.

Organ placement and communication

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What we’re trying to do now is we’re taking an organ and we’re trying to misplace it. We put it where it does not normally reside and then see whether that disrupts communication with its neighbouring organs.

We tend to think of all our organs as packed inside us to fit. If you think of the gastrointestinal tract, for example, there are all sorts of loops and there’s all sorts of twisting to pack it quite tightly inside us. Historically, we thought of that as the only way that a very long tube could fit into a body cavity. But now we’re beginning to think that there’s a bit of logic to that arrangement. This three-dimensional arrangement within us might matter in that the gastrointestinal tract communicates with adjacent organs.

A new dimension of biology

This opens up a new dimension in how we look at biology. I feel that we’ve been looking at something in a two-dimensional manner, and suddenly we zoomed out and we realised that there was this third dimension that we had not considered. We’d been considering the signal that this organ exchanges with that one, and we typically dissect these organs. Then they lose the three-dimensional arrangement. So we didn’t even know what these three-dimensional arrangements looked like until we started considering them within the body cavity.

As for the implications, we don’t know yet. It’s something that we’ll be exploring in the next few years. But at least for fruit flies, which we’ve been working on extensively, and male fruit flies in particular, this seems to matter for their fecundity and for their food intake. If we disrupt this crosstalk between adjacent organs, these male flies eat less, and they also produce less sperm. In this case, crosstalk is occurring between the gastrointestinal tract and the male gonad, which in fruit flies happen to be next to one another.

Plasticity beyond stem cells

The plasticity of adult organs has been particularly well studied in the context of adult stem cells. We know that our adult bodies have stem cells, and they replenish tissues and organs. For example, in the lining of our digestive system, we have these stem cells that replenish damaged cells, and that goes on in the background constantly.

We’re learning is that this plasticity extends far beyond the stem cells. So even the progeny of these stem cells, even these fully differentiated cells that we have in our body, are still capable of all sorts of plasticity. I find this kind of non-progenitor or mature plasticity quite interesting. And we know a lot less about this plasticity.

Developmental biology and physiology

A different way to think about developmental biology is to think about constraints and trade-offs, particularly in the context of the crosstalk between developmental biology and physiology. If we consider that organs continue to develop in an adult human, in an adult organism, then they must intersect with our normal physiology. For example, we eat certain kinds of food that deploy or redeploy particular developmental biology programmes that were deployed early on, and that takes you to a new kind of homeostatic setpoint. That generates a bit of a constraint. You’ve arrived there through this route, so now you have another set of directions in which you can go. And that will be determined by your environment again. So it’s very much a bi-directional mechanism.

At university, I had two books: I had my developmental biology book and I had my physiology book. I had different teachers teaching me those two subjects, and you end up with this kind of sequential view; first, you study developmental biology, and then you study physiology. But I think it’s very much a bi-directional crosstalk between the two. Developmental biology will give you a landscape in which you can respond to certain physiological inputs and those physiological inputs in turn will deploy a set of developmental biology programmes and not others. The crossover between the two is very much moving us between potential points, or to a specific point within a very broad landscape.

Which part of our body makes decisions?

Photo by Jose Luis Calvo

That is a very interesting question because historically, we thought of the nervous system: nerve cells are the clever ones in our body, and those are the ones that make all the decisions. I don’t question this, because obviously for any change in behaviour it really helps if you engage your nervous system, but I wonder whether the substrate – the place where metabolic decisions and physiological decisions are made – may be elsewhere.

Take, for example, the cells within the lining of the gastrointestinal tract. They’re going to sense a nutrient, and somehow, they’re going to maybe integrate that nutritional information with information about microbiota, information about the internal state. Then those cells will send a signal back to the brain. Maybe the ones that integrated all that information were actually the gut cells and not the nervous system. The nervous system would just be the effector of all the behavioural changes. But the decision maker, the smart cell in this particular example, might be the gut cell. It’s interesting to think of decision-making as a more diffuse property of our body rather than one solely focused on the nervous system.

Discover more about

how our organs change

Miguel-Aliaga, I., Hadjieconomou, D., King, G., et al. (2020). Enteric neurons increase maternal food intake during reproduction. Nature, 587, 455–459.

Ameku, T., Beckwith, H., Blackie, L., et al. (2020). Food, microbes, sex and old age: on the plasticity of gastrointestinal innervation. Current Opinion in Neurobiology, 62, 83–91.

How organs change and communicate