The probiotic bacteria engineered to treat diabetes

0:23Welcome back to the Nature Podcast. This week, a probiotic to treat diabetes. and what scientists are hoping to learn from today's eclipse. I'm Benjamin Thompson and I'm Nick Petra-Ciao.

0:45Researchers have developed a probiotic that can actively respond to high blood sugar levels, which they hope could one day be a new treatment for diabetes. So we thought there was an opportunity to develop a treatment that behaves more like the body itself and can respond to changes in glucose rather than simply delivering a fixed amount of medicine. This is Ninzi Guan, one of the team behind the new probiotic. Now diabetes is a pretty common condition. The WHO estimates that around 1 in 9 people live with the disease, the vast majority with type 2 diabetes, which is typically acquired late in life.

1:32In type 2 diabetes, the hormone insulin is either ineffective or produced at too low levels to control blood sugar. Over time, if blood sugar levels are left unchecked, this can lead to all sorts of complications, like kidney problems, blindness and even amputation of limbs. So management is really important. There are drugs that can manage type 2 diabetes. You've probably heard of GLP-1 agonists, for example, also known by their brand names like Azempic or Ouigavi. These medications can ultimately help stimulate insulin production and keep blood sugar levels in check. But there can be an issue with this.

2:14My major challenge is that blood glucose goes up and down throughout the day depending on meals, physical activity and many other factors. But most medicines are given at a fixed dose and on a fixed schedule. So there can be a mismatch between a treatment that is relatively fixed and a biological system that is highly dynamic. Diabetes medications such as glp1 agonists can have side effects too which can be exacerbated if they are given more than they are needed so nindsey and the team wanted to see if they could make something that just gave people medication when they needed it they decided to make a living drug and i mean that in every sense of the word rather than giving a fixed medication they wanted something that could respond to blood sugar levels.

3:13So they turned to probiotics, swallowable microorganisms. The team genetically engineered a strain of the bacterium E. coli that's commonly used in probiotic research, allowing it to sense glucose levels. When levels are high, the E. coli produces and releases GLP-1 molecules. A simple way to think about it is that the system has a molecular break. When glucose is low, that break keeps GLP-1 production switched off. When glucose rises, the bacteria generate a small signal. The signal releases the break, so the bacteria starts producing DLP1. As glucose comes back down, the signal decreases and the break is applied again, reducing or switching off DLP1 production.

4:15The team nicknamed their glucose responsive bacterium GIFT and tried it out in some animal models of diabetes, in this case mice and macaques. After giving the drug orally, they monitored the animal's responses. The animal results were very encouraging. One of the first things we wanted to know was whether the bacteria could really tell the difference between a high glucose diabetic state and a normal state. In mice, we found that the glucose responsive circuit was strongly activated under diabetic conditions. And this response led to GLP-1 production. The engineered gift cells significantly improved blood glucose control and glucose tolerance in diabetes mice.

5:08And when we then test the treatment in monkeys, which is physiologically closer to humans, we were very pleased to see improved glucose control in these animals. These results also showed that the orally taken probiotic was able to make its way through the stomach to the gut and still function. Nincy and the team also showed that GIFT seemed to help protect the animals against some of the complications associated with diabetes. The animals had less fat accumulation in the liver and lower levels of damage to the kidneys and colon, compared to the diabetic model animals that hadn't received GIFT.

5:50And that wasn't all. In the diabetic mice, treatment with GIFT led to a reduction in both body weight and body fat. So although the main purpose is to improve glucose control, the results suggest that it may also provide an additional benefit in reducing excess weight and fat accumulation. Such results may not be terribly surprising, given that GLP-1 agonists are often used for weight loss. But Ninji thinks that this could be helpful to people with diabetes who often have excess weight which can exacerbate their condition. And while these results may sound positive, Ninji cautions that GIFT is a long way away from human trials.

6:36She and the team want to understand more about how the bacteria behave, how long they remain active for example and therefore how often you'd need to take the probiotic. The team also need to ensure that the probiotic is perfectly safe, especially in the long term. But ultimately, they hope that this work could one day offer people with diabetes a reactive living drug that could help them easily manage their blood sugar without worrying about spikes or crashes. And if successful, they wonder if this kind of living drug system could be used for all sorts of diseases. In the longer term, we also hope that this idea can go beyond diabetes.

7:16The same kind of living platform could potentially be programmed to sense other disease-related signals and produce different therapeutic molecules when they are needed. So ultimately, our goal is not just to develop one treatment, but to explore a new regeneration of smart, self-regulating living medicines that can work more closely with the body. That was Ninjiguan from East China Normal University. For more on living drugs, head over to the show notes for some links. Coming up, how to safely see today's eclipse in the Northern Hemisphere. Right now, it's time for the Research Hourlights, read by Dan Fox.

8:07Mountain lions have been found to have an unlikely effect on driver safety, with research finding that motorists in areas where the animals are present are less likely to be in collisions with deer. Researchers cross-referenced data about where vehicles have hit Colombian black-tailed deer with GPS data from collared big cats and camera trap images. They found that the presence of mountain lions, also known as cougars or pumas, is associated with a 67 % reduction in the probability of a deer vehicle collision. Deer avoid roads when pumas are around, probably because forest edges, including roadsides, are prime hunting grounds for the big cats, and cougars are nocturnal hunters, which could encourage deer to become less active at night when many collisions occur.

9:00The team hope that highlighting this unexpected effect might help to build support for coexistence between humans and large carnivores. Hunt down that research in current biology.

9:17How does dripping water erode rock over time? New research suggests that each droplet acts like a tiny hammer, repeatedly damaging the surface in the milliseconds after impact. Previous studies of water droplets have relied on high-speed cameras, but this technique can't reveal how the force of each drip is distributed after impact. So researchers used a sensor that measures surface strain, the deformation of a material, below panes of glass and then took measurements as droplets rained down onto them. In the first two milliseconds after impact, the droplet induces a powerful force that can begin to fracture the surface material.

10:00Then, in the following 2 to 20 milliseconds, the material and water vibrate in sync at a frequency close to data which many rocks vibrate most easily. The authors say that these vibrations could expand microcracks and potentially increase erosion. Drop into the journal Small to read that research.

10:28Back in the 1600s, Isaac Newton did a very peculiar experiment where he sat in a darkened room to dilate his pupils and then looked at a reflection of the sun in a mirror now this didn't go too well for him he was essentially blind for several days and suffered quite severe arter effects for several months now i'm not a medical doctor but let me say this quite plainly do not stare at the sun it is very very bad for you now why am i telling you this listener well because there's quite an exciting astronomical event happening shortly after the podcast goes live today and it's a solar eclipse which will be visible either completely or partially over much of the northern hemisphere at peaks about 10 past 7 p.m here in the UK and here to tell us more about it is senior reporter here at Nature Lizzie Gibney.

11:23Lizzie how are you doing today? Hello Ben I'm good thank you I'm excited about the eclipse. So what will be seen and where will it be seen Lizzie? I I think if you're in Iceland or northern Spain, you get the most eclipse, if I put it like that. That's right. But in various places in the northern hemisphere, stuff can be seen. Yes. So if you're in the path of totality, that is when the moon completely obscures the sun, you're going to see the total solar eclipse. And that is going to be in, yes, parts of Greenland, parts of Iceland, northern Spain and Portugal. For much of the rest of Europe and some parts of the US and Canada, you're going to see a partial eclipse.

11:59And the further away you are from that line, less the sun is going to be obscured. So for instance, here in London, it's going to be about 90%. And in the very far southwest of the country, you'll get up to 95%. Over the rest of Europe and little parts of North America, there will be some potential. So for example, in New York, it'll be about a 10 % eclipse, so not huge. And the maximum will be just before two in the afternoon. And so for folk who are maybe heading out to see what's going on, how can they do it safely. That's most important. Yeah, it's really important. I didn't know that story about Isaac Newton.

12:31So yeah, you can get terrible retinal burns, like permanent damage from looking at the sun. And one of the problems is, of course, you want to see the sun because it's an eclipse. And during a partial eclipse, a lot of the sun is covered. And so the rays are kind of dimmed, especially if it's in the evening, it's towards the horizon. So it might feel like there isn't any damage happening. You might not have your natural reaction to flinch away from the sun, and that kind of protective measure your body takes, but actually it is doing quite severe damage. So, you know, almost every eclipse, there is always afterwards a record of people who do get injured, unfortunately.

13:06So make sure that's not you. And there are various ways. One is to have eclipse glasses, which given this is coming out on the day of the eclipse, people, if they don't have them already, may struggle to get hold of, but they have very, very heavy filters and And they only let through 0.0032 % of UV and visible light. So teeny, teeny tiny maps. So if you're wearing them, you actually can see absolutely nothing of the everyday world, as I've found when I'm testing them out. But if you look up at the sun during the eclipse, you're going to be able to see, you know, the kind of crescent shape as the moon obscures the sun, as we are kind of in the moon's shadow.

13:42And they have to adhere to very specific ISO standards. So make sure you've got exactly the right ones. if you want some DIY methods I have those as well if perhaps you haven't prepped ahead so what you are going to be able to do with the DIY methods is get a projection of that image again exactly that kind of one circle crossing on top of the other creating that kind of crescent shape and to do that you make a kind of pinhole camera like your own DIY home version and it can be as simple as two pieces of paper you put a pinhole in one you know it could be a pinhole you hold one sheet up so your back is to the sun but you hold a sheet up so the light can fall through that hole and then you hold another piece of paper out around arm's length in front of you and you will get the image projected onto that piece of paper you'll get a little inverted kind of crescent shape and you can play around with it until you know you get the best version of that right i think that's what i'm going to do but there is another alternative right to use a colander some people might call it a strainer basically a common kitchen implement that's right so the other thing i should have said as well is because it is going to be quite low in the sky because it's happening in the evening across Europe.

14:48So you've got to check you actually will have line of sight of it from wherever you are. I'm going to go out to a park because it's quite a nice space, like open space. So I'm going to be taking with me half of my kitchen because you can also use a colander, which is actually really nice. I've not tried it yet myself, but from what I can see, because there are lots of little holes, effectively you get like a kind of a disco ball like effect where you get lots of different little inverted images. Along the same theme, I've read that you can use a slotted spoon. Basically, you need some kind of aperture for the light to go through.

15:23And if you are just out and about, if you have literally nothing, you've completely forgotten, you don't have anything with you, the very easiest option is to find a tree that you can stand beneath, like a canopy of leaves, and that, you know, you get those just like teeny tiny little gaps where the sunlight falls between the leaves in a canopy. That also can act as your pinhole. And if you look on the ground, you should hopefully be able to see exactly that crescent again. So indirect is the way forward if you haven't bought the necessary gear ahead of time. Do not look directly at the sun. Precisely.

15:55There is no safe way of doing it. You can't reflect it off anything. Definitely don't look through binoculars or any kind of telescope like that. In fact, leave all that side to the professionals. People will be using telescopes to look at it directly, but with very, very specialist filters on them, which are absolutely essential. So yes, unless you have the glasses which have the right ISO mark on them, then do one of these projected methods. And I think you can have a lot of fun. Because the whole thing lasts about two hours, you have an hour of the moon kind of moving over the sun and an hour as it's moving off.

16:25That's when we're in a partial eclipse. When you have totality, which is what's going to happen in parts of northern Spain, Italy, Iceland and Greenland, then there is that, you know, kind of like minute and a half, two minutes of totality where the whole world goes dark. You don't have to bother looking up at the sky and trying to find ways to see the actual eclipse. Like what's weird and wonderful is this idea that it's just suddenly nighttime when it should be daytime. The birds go really quiet, stuff like that. Yeah, how the animals react, how colors change, what kind of shadows you can see, what your fellow humans are doing.

16:56Maybe just take pictures of your friends and family in that moment rather than necessarily the eclipse itself. That's definitely a lot safer. So right, aside from it being quite a peculiar event in terms of what may be seen. Scientists are, of course, very interested in these things. What will they be looking for? Absolutely. So the key thing that you can do during eclipse that you can't do normally is see the sun's corona. So that's this kind of magnetic atmosphere that is around the sun, extremely hot. But of course, normally it's hard to see what's happening at the edges because the sun itself is just so bright that it obscures absolutely everything else.

17:33It completely makes that impossible. But as soon as you've got something in front of the sun, you can see the corona. And that's actually something you would be able to see if you're in totality. And you can see, for instance, sunspots where it's slightly dipped or there's potential to see flaring and activity. So that's hugely interesting for scientists to see to the extent that there is actually an ESA mission called Probe 3 that is doing this effect artificially. So they have two spacecraft orbiting Earth where one acts as the fake moon and the other one is the fake Earth. and they observe the sun in that way.

18:06So this is so useful for scientists that we've set up a whole bevy of telescopes in space who are trying to study this. But this is one of the rare opportunities we're able to do it from Earth. Right, because it's weird. The surface of the sun is about, what, 5 ,000 degrees Celsius. But the corona is, what, a couple of million? And it's the gap between the two that is confusing. Absolutely. And the corona is where we get a lot of the solar radiation comes from, which we care hugely about here on Earth. We call it space weather. We get streams of charged particles coming off the sun and they can affect train lines and electricity networks and disrupt satellites.

18:42So it's something that scientists are really trying to better understand is the activity of the sun's corona and maybe how we can better predict the activity. And to do that, we have to understand the corona a lot better. And so, yeah, eclipses are an absolutely brilliant way to be able to study it from Earth. Well, I am very excited to go out and see what I can see on Wednesday evening, indirectly and safely, of course. And listeners, we'll have an article talking even more about the science that can be done during an eclipse. So look out for a link in the show notes for that. But for the meantime, all that's left to say is Lizzie Gibney, thank you so much for being here.

19:16Thanks so much, Ben. and that's all for this time if you'd like to stay in touch with us you can we're on email podcast at nature.com or you can find us on social media at nature podcast i'm nick petra and i'm benjamin thompson thanks for listening