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Spot the differences: how fly droppings teach us about digestion

3 Nov, 2011

What can fly poo tell us about digestion and nutrition? And how? Paola Cognigni tells us why her lab studies Drosophila.

In ancient times, the diagnosis for diabetes was a sweet taste in the patient’s urine – mellitus, honey-sweet, is the term we still use to refer to the most common forms of this disease. To the relief of physicians everywhere, more sensitive tests exist today that don’t require the ingestion of any bodily fluids. But it is still true that we can learn a lot about a body and its health by knowing what comes out of it.

Our lab is one of several in the world using the fruit fly, Drosophila melanogaster, to find out more about digestion, nutrition and how the body changes in response to differences in diet. Too small for blood tests and unresponsive to surveys, the little fruit fly is still an incredibly powerful system for scientists: more than 100 years of research have led to the development of an unparalleled set of methods to control genes, cells and organs. Single neurons can be turned on and off in response to a flash of light, genes can be shut down one by one, and many tests can be applied to test their preferences, memories and health.

However, we wanted a system to monitor the flies’ body functions without damaging or disturbing them. We went back to the idea that looking at what the body throws out as waste can tell us a lot about what it’s doing – being much like a nosy neighbour rummaging through the waste bins.

Fruit fly droppings coloured with a dye in the food, from a normal fly (left) and a fly with a surge of diuretic hormone (right): the increase in fluid makes the spots look lighter

As fly droppings are just tiny transparent droplets, we added a dye in their food that goes through their gut and comes out with the waste as coloured spots. Simply looking at these spots already tells us a lot about the fly’s state: the more the fly eats, the more coloured spots we can see on the clear surface of their cages.

The colour of the dye changes based on the acidity, which is different depending on what the flies have been eating. When water is scarce, the dye is more concentrated and the spots are darker, while watery droppings are light. So, when we use genetic techniques to cause a sudden release of diuretic hormone, fluid is excreted in large amounts and the spots become much paler.

A normal fruit fly (left) and a fly with extreme water retention (right), caused by shutting down the diuretic hormonal system. The flies' gut full of blue food is visible in their abdomen.

These genetic manipulations can be applied in many ways to test how important each organ, gene and biological process is to the overall wellbeing of the animal. As our technique lets us keep an eye on the flies without disturbing them, we can also see what happens to them over time when we apply these manipulations and change their internal regulation. So, if their diuretic system is shut down, not only do we get darker spots, but the flies balloon up from extreme water retention. This way, we can test not only what the diuretic system is doing – regulating how much fluid remains in the body and how much is excreted – but also why, and what happens if it’s not working properly.

Droppings of a female fruit fly before (left) and after (right) she has mated with a male fruit fly and has started producing eggs. The driest droppings are thin elongated rods rather than droplets.

Situations in which these processes in the body start behaving differently are not always a sign of unhealthy imbalance, or the work of meddling scientists. Darker spots also appear when a female fly mates with a male and starts producing large amounts of eggs – in fact, their droppings are so dry that they are no longer droplets but long extruded rods, meaning that the flies are retaining a great part of their water. This is because providing for the developing eggs requires extensive resources from the mother, who has to divert many of her nutrients and fluid to keep the growing progeny fed and moist. If this sounds familiar to mothers and mothers-to-be, it’s not a coincidence: providing for a growing human is no less demanding, and just like in flies, water retention and constipation are common in pregnancy.

A remarkable parallel between flies (left) and the head of the Miguel-Aliaga lab (right): similar changes happen in the body during egg production and pregnancy.

In the end, a fly’s life and a human’s are less different than we’d perhaps like to think. In a body the size of a mustard seed, the fly houses a tiny version of a brain, gut, and excretory system. Their food choices are much like ours – as you may have noticed when small winged visitors appear around your kitchen waste. What they decide to eat and what their body does with these nutrients can give us clues to what drives our own appetite and cravings, and to why certain foods affect our weight, health and mood differently from others.

We have found a simple way to gain a lot of information about a fly’s internal state and how it’s affected by changes in the environment or within their own body. We can then use the many genetic techniques that exist in this animal to find out how and where these effects are happening and how they can be changed, something that would be impossible to do in humans. We hope this will help us shed light on the internal workings of our digestion, appetite and metabolism. Sometimes the answers can be found in the most unlikely of places – for us, this turned out to be a fruit fly’s rear end.

Paola Cognigni

Paola Cognigni is a research student working in the lab of Wellcome Trust Research Career Development Fellow Dr Irene Miguel-Aliaga at the University of Cambridge.

You can see more of Paola’s images in this post and read about their research findings on the Wellcome Trust website.

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