Breath-Taking Science- How Intestinal Breathing Could Save Lives - Science View

In rural Japan, dojo loaches can be found just about anywhere. But did you know that these loaches have a special ability? They can breathe not only through their gills but also through the intestines. This raised the question, could humans have a similar ability? The researcher who explored this idea was Professor Takanori Takebe from the Institute of Science Tokyo. He's a leading scientist who successfully created mini livers or liver organoids from iPS cells and holds key positions at multiple research institutions in both Japan and the U.S. During the COVID-19 pandemic, hospitals struggled with a surge of patients experiencing severe breathing difficulties. To help these critically ill patients, specialists across disciplines from clinical medicine to mechanical engineering gathered under Takebe's leadership to explore new solutions. Finally, it was confirmed that even pigs that have organs similar to humans can absorb oxygen through their intestines. This fascinating discovery earned the Ig Nobel Prize, an award celebrating research that sparks curiosity and humor. Now further research is underway to explore how it could be applied to humans. This is a completely new approach to saving patients with severe breathing difficulties. We'll bring you the story of this groundbreaking challenge. Breathing is one of the most important functions of life and most people assume that it only happens through the mouth and nose. But did you know that it's also possible to breathe through the intestines? This surprising discovery was proven in an experiment with pigs and the study received the Ig Nobel Prize, an award that celebrates fun and unusual achievements in scientific research. And this breathing using the intestines may also become a new means of saving people with serious illnesses. Today we'll be speaking in depth with Professor Takanori Takebe of the Institute of Science Tokyo who led this research. Hello, thank you very much for having us today. Hi, welcome to our university. And this place is really beautiful. I didn't know that this university had such a beautiful view. I really enjoy this, you know, beautiful view. For example, you can see the sky tree over there and on the left hand side you can see Ueno National Park and there are many universities you can see. It's a beautiful place. So this place, by the way, was the Institute of Science Tokyo. It's a newly established school, right? So it came from a merger of the Tokyo Medical and Dental University and Tokyo Institute of Technology, right? So what are your thoughts about this merger? It's quite an exciting time. You know, many medicines can be accelerated by engineering principles. So this university merger really triggered interdisciplinary collaborations. First of all, congratulations on winning the Ig Nobel Prize in 2024. And I have the impression that the Japanese researchers often receive this award, but I don't know much about it. Could you tell us a little bit about it? Yeah, I think that, you know, it's kind of parody of real Nobel Prize, but IG Ig Nobel Prize is something with a sense of humorous and, you know, make people laugh and then, you know, inspiring many people. So that is actually the foundational concept of the Ig Nobel Prize, which is a little, you know, funny. But if you want to do something new, I think we probably need to consider a very different perspective that, you know, potentially comes with a little weird stuff as well. So I think, you know, Ig Nobel Prize is capturing some aspects of human creativity. Media was very having lots of fun with it as saying, butt breathing. And what animal gave you this idea? You know, a species of the fish called loaches. So in Japanese, dojo, and dojo is actually also internationally known. So when we started the research about this project, you know, the resources, including like, you know, grant funding, as well as, you know, people who are involved is extremely limited. Only just one student working with a very limited, you know, amount of budget to just to perform initial explorations. One of Takebe's research hubs is Yokohama City University. In 2017, a student inspired by Takebe spent countless hours in the same lab. Ryo Okabe was at the time a graduate student at Kyoto University who specialized in thoracic surgery. Okabe has loved animals since he was a child. His bookshelf was always filled with illustrated reference books. One day, he showed Takebe a book. Inside it was a photo of a dojo loach. Dojo loaches live in muddy waters. Like most fish, they normally breathe through their gills on the water. However, when the oxygen level drops, they rise to the surface, inhale air, and absorb oxygen through the intestines. The bubbles they release are excess air, or in other words, farts. Intestinal breathing was a completely new idea, something Takebe had never considered before. I think I can do it. I've been studying fire extinguishers for a long time, so I can see the potential of fire extinguishers from many perspectives. I think I can do it. At the time, only Takebe was interested in it. I've consulted many people about it. I have a lot of these bookshelves. When I look at these bookshelves, I feel like it's not a paper. Everyone thinks it's a joke. But that's what I usually don't think about. Could other animals also have the ability to breathe through the intestines? With Takebe's encouragement, Okabe set out to conduct experiments using mice all alone. He used perfluorodecalin, or PFD, a stable liquid with high oxygen solubility. It was infused with oxygen and delivered into the mouse's intestines through the rectum. Results of the mice experiments showed that the oxygen levels in the bloodstream increased significantly, confirming that the intestines could indeed take in oxygen. Later, Okabe left the lab and went on to become a home care physician. But the research on intestinal breathing was carried on by other members of the Takebe lab, and they brought it up to the next level. And you've moved on so far that it will also lead to saving people, right? Yeah, so this is another sort of serendipitous moment we had, because we had very devastating challenges in the past few years, as many of you have known about the COVID-19 pandemic. During the COVID-19, a lot of people were in need of like ECMO, and a lot of those medical equipments were needed, but it wasn't in handy in many places. So many people lost their lives too. Exactly. So I think we realized, you know, such a, you know, very high level interventional strategies is really, you know, limited in a sense for accessibilities. But this intestinal breathing method, if applied, we can simply inject the, you know, oxygen liquids from the butt so that we can simply support the respiratory failure condition. You know, maybe some patients caused by COVID-19 or even other, you know, disease, maybe we can help out. So that sort of like, you know, societal challenge is really pushing our program forward. In 2020, the COVID-19 pandemic spread across the world. It pushed healthcare systems to the brink. For patients suffering from severe respiratory failure, the key treatment was ECMO, which acts as an artificial lung by supplying oxygen to their blood. However, ECMO was difficult to operate, and the number of machines was limited. At Nagoya University Hospital, the situation was dire. Dr. Tasuku Fujii, an ECMO specialist, was overwhelmed with critical cases in the ICU. This experience led Dr. Fujii to explore the potential in intestinal breathing and join Professor Takebe's research project. Under Dr. Fujii's leadership, a team conducted a series of experiments using pigs, which have organ structures similar in size and function to humans. The pigs were placed in a slightly oxygen-deprived state. For future human applications, the oxygen-infused PFD solution was placed in a pouch similar to an IV drip. A manufacturer specialized in enemas handled the PFD filling process. In a clean room, the liquid was dispensed in precise amounts. This enabled the mass production of clinical pouches. The perfluorodecalin, or PFD, will be administered through the pig's rectum. 5, 4, 3, 2, 1 To ensure reliability, the experiment was repeated multiple times while closely monitoring oxygen saturation level. As a result... With promising pig trial results, human clinical trials began at a hospital in Osaka. The first phase tested the safety, injecting PFD without oxygen in healthy volunteers. What began from a simple illustrated reference book is now moving toward human applications. So your experiments using pigs helped your research advance really quickly? Yeah, totally. We could confirm our findings with tens of, you know, twenties of pig experiments to show that intestinal breathing methods can be effectively translated in a human-sized pig model. So that has actually convinced us to move on to conduct the clinical studies in the end. It's only three years after the pig experiments that you have started human clinical trials. And compared to the IPS cell research that you, which is your main field, this is incredibly fast, I believe. Why is it so fast? Yeah, the materials we are using is already applied in a medical situation in a history, actually. For example, like, you know, maybe 20 years ago, the same, you know, medical sort of device was actually used in different applications. So we kind of repurposed existing medically qualified materials for these breathing methods. The key is ease of use. So what we need is simple liquids that can carry oxygen. And then we also need oxygenation, you know, tank, so oxygen gas. So these two components is the essential components, which is actually available in many different places, even in an ambulance process. So with these, you know, two materials, you can simply inject. Wonderful. So that also means that there's lower risks as well. Yeah, I wouldn't say lower, but, you know, the risking process, risk reduction process is actually much more efficient, just because of, like, you know, past, you know, discoveries, available know-hows and knowledges. A pharmaceutical company, along with a startup founded by Takebe, conducted a clinical trial. On this day, Takebe was in a meeting. Clinical trials and experiments require significant funding, so they constantly negotiate with various organizations to secure investments. Then, there was a meeting to determine the direction of the next clinical trial. Now preparations began for the next phase, testing the treatment on patients with breathing difficulties. To take in oxygen more efficiently, Takebe also sought the expertise of mechanical engineering specialists. Professor Tadahiko Shinshi has been involved in the development of medical devices such as artificial hearts. His team developed a robot according to Takebe's request. It automatically moves through the large intestine. The robot is designed to spread oxygenated PFD throughout the entire 1.5 meter long large intestine, aiming to increase oxygen intake. It uses air pressure changes to perform a twisting motion, letting it move deeper inside the intestine. Once the robot reaches the end, it seals off the large intestine with a balloon. Then the robot infuses the PFD. An experiment was conducted to insert the robot into a pig. At first, it was manually pushed in without using air pressure. Next, when it was turned on, the robot automatically started moving. The robot's progress was monitored using x-rays. From the anus, it was manually pushed into the large intestine. As you can see, it was pushed in to a certain extent. But at the end, it got stuck in the large intestine. This is where the robot changes the air pressure to perform a twisting motion, and the robot slowly enters the large intestine. You can see the robot slowly entering the large intestine when it passes through the This is how the robot changes the air pressure to perform a twisting motion, and the robot slowly enters the large intestine. In the case of ECMO, you need a technician to use the robot, but not every hospital has one. However, in the case of ECMO, it is relatively easy to insert the robot into Wow, I was really, really surprised with this. A robot that releases oxygen inside the intestines has also been developed. This kind of collaboration between medicine and engineering may be one of the benefits about the founding of the Institute of Science in Tokyo, right? This collaboration actually happened before the University of Mergers, but definitely this Institute of Science Tokyo is actually helping to drive this type of medical engineering collaboration processes. So I usually value many inputs from the different practices, different disciplines. For example, in this case, we just started the collaboration after this random conversation, and it eventually made it fruitful because we are already making a prototype for doing that. So I think there are ways to approach the problem with the multidisciplinary collaboration is really our driving force for innovative type of works, and I really enjoy that. Also, other ways to use this technology besides emergency medical care? I'm actually working in Cincinnati Children's Hospital where we saw many young kids or even neonates having some very critical challenges. They're currently even in the neonatal kits with the respiratory problems, we only do mechanical ventilation, tubing it into the lung to help the oxygenation. But on some instances, they cannot, even with the mechanical ventilations, oxygen is not sufficient. So for that case, there are not any other ways to help out. Many wider range of the disease is actually putting kids' life endangered because of the oxygenation problems. So if we can develop the methods more widely accessible to many different kids, I think that would be a very rewarding path as a scientist. Takebe spends more than half of the year at the Center for Stem, Cell and Organoid Medicine at Cincinnati Children's Hospital in the U.S., conducting research on many livers. Through his work, he often meets children battling illnesses, which has given him a deep appreciation for the value of life. His work has inspired a growing number of researchers. This is the Neonatal Intensive Care Unit at Nagoya University Hospital. Premature newborns often need oxygen support from ventilators to help them breathe. However, long-term use of ventilators can damage the lungs or lead to infections. Thus, doctors are required to carefully manage each baby's breathing. Now, intestinal breathing is gaining attention among pediatricians as a promising new approach. Led by Professor Takebe, the team of researchers from a wide range of fields is joining forces to develop a new technology to explore the potential of intestinal breathing with hopes of saving countless lives.