Ученые Монашского университета создали 3D-модели кишечника для разработки персонализированного лечения воспалительных заболеваний

Melbourne researchers create intestinal models to research inflammatory bowel disease In short: Researchers at Monash University say they are a step closer to broadening their understanding of inflammatory bowel disease (IBD). IBD encompasses chronic autoimmune conditions, including Crohn's and ulcerative colitis, which involve inflammation in the gastrointestinal tract. For the first time, using human samples, scientists have developed tiny 3D models of paediatric IBD patients' intestinal lining, alongside its accompanying bacteria. Ronan Somers looks like any other 12-year-old boy, but he has been battling a hidden illness. At times, his ulcerative colitis has stopped him from doing the things he loves. "I couldn't do a lot of stuff because I felt very tired," he said. "It just made my stomach hurt and cramp and when I tried to do exercise it would hurt, and I'd go to the toilet six times a day, and that was really hard for me." Ulcerative colitis is one of the two major types of inflammatory bowel disease (IBD), the other being Crohn's disease. It is marked by inflammation and ulceration in the large intestine, causing at times painful and debilitating gastrointestinal symptoms. There is no cure, but it can be managed with medication. Ronan has missed one in five days at school this year due to illness and medical appointments. The road to diagnosis and then finding the right treatment has been long and difficult. "It was a disease we'd never heard of before, so it was a new journey to us," Ronan's mother Jasmin Alarcon said. She said it took 904 days after diagnosis for doctors to finally pinpoint the treatment that would work for him. "He went on a lot of medication that didn't work, so it was a bit of a of trial-and-error stage," she said. Researchers create 'mini guts' Ronan's long journey to remission — a state of having symptoms under control — is a common trajectory that scientists at Monash University are hoping to turn around. For the first time, using human samples, they have developed tiny 3D models of individual paediatric IBD patients' intestinal lining, stored separately to and alongside its accompanying bacteria. The organoids, nicknamed "mini guts", are a game-changing research tool. "The benefit is it allows us to study the disease in living tissue in the lab so we don't have to go to the patient, but it also allows us to develop and test new therapies," lead researcher Helen Abud said. Researchers have also been able to create technology to inject that same gut bacteria into the patients' organoid models, something that gives paediatric gastroenterologist Associate Professor Edward Giles optimism. "[We can] really try to understand in a very detailed way the interaction between the bacteria and the lining of the bowel to see if we can understand what's driving inflammation and also understand potential new targets for treatment," Dr Giles said. The hope is that the advancement will enable research that leads to more precise and tailored treatments for patients. "We're starting to have great ability to understand some of the complexity in this disease because, unfortunately, it is complex and very individual," Dr Giles, who co-authored the research paper, said. "We do have good treatments, but there is a huge onus on patients to go through this process, and we aren't very good at targeting the right treatment to the right patient at the beginning of their journey." The team has created a "living bio bank" of several different organoids, based on several different patients. "The overall goal is to find the best treatment for each individual patient so we need to have a replica of a whole diversity of individual patients," Professor Abud said. "And this patient population is from our local paediatric Australian patients, so it's going to be relevant to patients that are being treated here." IBD prevalence growing Australian National University School of Medicine and Psychology Emeritus Professor Paul Pavli described the research as "exciting". "It is a very important study. It's meticulous work, it's painstaking and it's going to provide very valuable insight into the cause of some of these diseases," he said. "This is early days yet, but the point is they're beginning to tease out how normal bacteria and how the bacteria that are obtained from Crohn's and colitis patients cause abnormalities in both normal mini guts and mini guts derived from Crohn's and colitis patients." Dr Pavli, who also works as a consultant in gastroenterology at Canberra Hospital, said it would enable medical professionals and researchers to understand the basic mechanisms of how the bacteria and the lining of the gut cause inflammation, and could lead to personalised medical care. "This is leading towards personalised medicine where you can actually identify the things that go wrong that cause inflammatory bowel diseases in such patients," Dr Pavli said. "It's not something that's going to develop in the next two or three years or even five years. It's going to take some time to develop the techniques to be able to provide any sort of personalised medicine." IBD is estimated to affect about 180,000 Australians, and for reasons experts are not yet able to explain, that number is on the rise. By about 2030, the number of sufferers will amount to 1 per cent of the population. The statistics are alarming for advocates such as Leanne Raven, the chief executive at Crohn's and Colitis Australia. "In Australia, the prevalence and the incidence is just compounding," Ms Raven said. "We are worried because there are so many barriers to people getting diagnosed and then getting into remission. "For about half of the people who are diagnosed, it can take five years to get them into remission after diagnosis." She said a recent study by her organisation found of all chronic conditions, IBD had the lowest investment in research. "Being able to use technology to play around and test different things and see what response you get is fantastic, really innovative work," she said. "Research is our hope for the future." It is something Dr Pavli agreed with, but he said the field did not receive much funding. "Crohn's and colitis are not sexy diseases," he said. "They're not the sorts of conditions people have heard about because … it's not dinner party conversation, so from that point of view there's not a great deal of public awareness about them. "These conditions are quite serious conditions affecting young people significantly and anything that provides some insight into what goes wrong is going to lead to better treatments."