Latest news with #ScienceImmunology
Yahoo
3 days ago
- Health
- Yahoo
Researchers find a link between gut bacteria and genes in colitis flare-ups
Researchers have identified a gut-genetic interaction that could trigger an overactive immune response in the colon — offering one possible explanation for the pain and bleeding of ulcerative colitis, and why it behaves so differently from patient to patient. Their research is published Friday in the journal Science Immunology. Ulcerative colitis is a chronic disease that affects more than 1.2 million people in the United States, according to a 2023 study of medical claims data. It falls under the umbrella of inflammatory bowel disease, or IBD — a group of conditions that includes Chron's disease and is marked by unpredictable flare-ups, long-term discomfort, and treatments that often work inconsistently. 'This study demonstrates that it's not just an imbalance of microbes in your gut or genetics that induce intestinal inflammation — but the interaction between the two,' said Hisako Kayama, an associate professor of immunology at Osaka University and co-senior author of the study. At the center of that inflammatory response is a protein called STING that helps the body recognize the DNA of bacteria and viruses and mount an immune response. Healthy people are able to keep this response under control with the help of a gene called OTUD3, which acts as a biological brake. But in some people, their OTUD3 gene variant leads that brake to fail — causing the immune system to treat harmless bacteria as a threat. Unchecked, the protein can drive chronic inflammation, particularly in the gut, which is home to many different types of "good" bacteria. The protein STING is very important in fighting bacterial infections, said co-author Dr. Kiyoshi Takeda, a professor of immunology at Osaka University. 'But the problem is that the overactivation of STING causes inflammation.' To explore how this interaction plays out, the researchers studied mice bred specially to have a genetic vulnerability to colitis similar to humans. When feces from the ulcerative colitis patients was transferred to the colons of the mice, they developed more severe colitis symptoms than mice with a normal version of the gene. If they didn't have the gene variant or the microbial trigger, the disease didn't develop. In total, researchers used tissue and gut bacteria from 124 patients — including 65 with ulcerative colitis and 59 with colorectal cancer — plus 12 healthy people as controls. The culprit was a molecule called cGAMP, which is made by certain gut bacteria. In healthy mice, researchers know that OTUD3 helps break down excess cGAMP so the immune system doesn't overreact. But in mice without a working version of that gene, cGAMP built up, overactivating STING and causing inflammation. The findings could help explain why some patients respond poorly to current ulcerative colitis treatments, which typically suppress the immune system as a whole. By pinpointing a single inflammatory pathway, the study opens the door to more precise, personalized therapies — especially for patients who carry this specific gene variant. Still, the researchers caution that any treatment targeting the STING protein directly must be used carefully, since suppressing it too much could leave patients vulnerable to infection. Alternative approaches, such as targeting cGAMP-producing bacteria, could allow STING to keep doing its job in the rest of the body while dialing down inflammation in the colon. The variant gene that colitis sufferers have is common. According to past genome-wide studies, it appears in about 53% of Europeans, 52% of Americans and 16% of Japanese people. Not everyone with it develops the disease, lending credence to the idea that it's the interaction between genes and microbes that triggers inflammation. 'This study is helpful in demonstrating a specific example — a genetic variant and a microbial signal — that leads to inflammation,' said Dr. Jonathan Jacobs, a gastroenterologist and microbiome researcher at UCLA who was not involved with the study. 'That's exciting," he said, because it offers a clear mechanism that ties together many of the risk factors scientists have long observed in inflammatory bowel disease. Even if it turns out not many people are vulnerable to this particular gut-genetic interaction, he said, the research could lead to more personalized treatment. 'It moves us closer to precision medicine,' Jacobs said. The shift toward more targeted treatment could make a world of difference for patients like Anderson Hopley, a volunteer with the Orange County and Los Angeles chapter of the Crohn's and Colitis Foundation who was diagnosed with Crohn's this year. 'I know people who have medication that'll work for a couple years, maybe even just a couple months, and then it kind of randomly stops,' he said. 'They have to adjust everything.' Although Hopley has Crohn's, not ulcerative colitis, he said the new study still resonates. 'I think it'd be really nice to know what causes this,' he said. 'Even if there's not a cure yet, just having an answer — some clarity — would be a step in the right direction.' This story originally appeared in Los Angeles Times. Solve the daily Crossword
Los Angeles Times
3 days ago
- Health
- Los Angeles Times
Researchers find a link between gut bacteria and genes in colitis flare-ups
LOS ANGELES — Researchers have identified a gut-genetic interaction that could trigger an overactive immune response in the colon — offering one possible explanation for the pain and bleeding of ulcerative colitis, and why it behaves so differently from patient to patient. Their research is published Friday in the journal Science Immunology. Ulcerative colitis is a chronic disease that affects more than 1.2 million people in the United States, according to a 2023 study of medical claims data. It falls under the umbrella of inflammatory bowel disease, or IBD — a group of conditions that includes Chron's disease and is marked by unpredictable flare-ups, long-term discomfort, and treatments that often work inconsistently. 'This study demonstrates that it's not just an imbalance of microbes in your gut or genetics that induce intestinal inflammation — but the interaction between the two,' said Hisako Kayama, an associate professor of immunology at Osaka University and co-senior author of the study. At the center of that inflammatory response is a protein called STING that helps the body recognize the DNA of bacteria and viruses and mount an immune response. Healthy people are able to keep this response under control with the help of a gene called OTUD3, which acts as a biological brake. But in some people, their OTUD3 gene variant leads that brake to fail — causing the immune system to treat harmless bacteria as a threat. Unchecked, the protein can drive chronic inflammation, particularly in the gut, which is home to many different types of 'good' bacteria. The protein STING is very important in fighting bacterial infections, said co-author Dr. Kiyoshi Takeda, a professor of immunology at Osaka University. 'But the problem is that the overactivation of STING causes inflammation.' To explore how this interaction plays out, the researchers studied mice bred specially to have a genetic vulnerability to colitis similar to humans. When feces from the ulcerative colitis patients was transferred to the colons of the mice, they developed more severe colitis symptoms than mice with a normal version of the gene. If they didn't have the gene variant or the microbial trigger, the disease didn't develop. In total, researchers used tissue and gut bacteria from 124 patients — including 65 with ulcerative colitis and 59 with colorectal cancer — plus 12 healthy people as controls. The culprit was a molecule called cGAMP, which is made by certain gut bacteria. In healthy mice, researchers know that OTUD3 helps break down excess cGAMP so the immune system doesn't overreact. But in mice without a working version of that gene, cGAMP built up, overactivating STING and causing inflammation. The findings could help explain why some patients respond poorly to current ulcerative colitis treatments, which typically suppress the immune system as a whole. By pinpointing a single inflammatory pathway, the study opens the door to more precise, personalized therapies — especially for patients who carry this specific gene variant. Still, the researchers caution that any treatment targeting the STING protein directly must be used carefully, since suppressing it too much could leave patients vulnerable to infection. Alternative approaches, such as targeting cGAMP-producing bacteria, could allow STING to keep doing its job in the rest of the body while dialing down inflammation in the colon. The variant gene that colitis sufferers have is common. According to past genome-wide studies, it appears in about 53% of Europeans, 52% of Americans and 16% of Japanese people. Not everyone with it develops the disease, lending credence to the idea that it's the interaction between genes and microbes that triggers inflammation. 'This study is helpful in demonstrating a specific example — a genetic variant and a microbial signal — that leads to inflammation,' said Dr. Jonathan Jacobs, a gastroenterologist and microbiome researcher at UCLA who was not involved with the study. 'That's exciting,' he said, because it offers a clear mechanism that ties together many of the risk factors scientists have long observed in inflammatory bowel disease. Even if it turns out not many people are vulnerable to this particular gut-genetic interaction, he said, the research could lead to more personalized treatment. 'It moves us closer to precision medicine,' Jacobs said. The shift toward more targeted treatment could make a world of difference for patients like Anderson Hopley, a volunteer with the Orange County and Los Angeles chapter of the Crohn's and Colitis Foundation who was diagnosed with Crohn's this year. 'I know people who have medication that'll work for a couple years, maybe even just a couple months, and then it kind of randomly stops,' he said. 'They have to adjust everything.' Although Hopley has Crohn's, not ulcerative colitis, he said the new study still resonates. 'I think it'd be really nice to know what causes this,' he said. 'Even if there's not a cure yet, just having an answer — some clarity — would be a step in the right direction.'
RNZ News
25-05-2025
- Health
- RNZ News
Daylight can boost the immune system's ability to fight infections
By Chris Hall * of How does the immune system know when it's daytime? File photo. Photo: Unsplash Ever found yourself out of sync with normal sleep patterns after late nights or working a night shift? It could be you're experiencing what scientists call social jet lag. The term describes the misalignment between our internal body clock (circadian rhythm) and our social schedule. Social jet lag associated with irregular sleep patterns and inconsistent exposure to daylight is increasingly common, and has been linked with a weakened immune system. Disruption of our circadian rhythms through shift work, for example, has been shown to have a negative impact on our ability to fight infections. These observations reinforce the idea that maintaining a robust circadian rhythm through regular exposure to daylight supports a healthy immune system. But how does the immune system know when it's daytime? That is precisely what our research, published today in Science Immunology, has uncovered. Our findings could eventually deliver benefits for the treatment of inflammatory conditions. Circadian rhythms are a fundamental feature of all life on Earth. Believed to have evolved some 2.5 billion years ago, they enable organisms to adapt to challenges associated with the 24-hour solar day. At the molecular level, these circadian rhythms are orchestrated through a genetically encoded multi-component time keeper called a circadian clock. Almost all cells are known to have the components for a circadian clock. But how they function within different cell types to regulate their behaviour is very poorly understood. In the laboratory, we use zebrafish - small freshwater fish commonly sold in pet stores - as a model organism to understand our immune response to bacterial infection. We use larval zebrafish because their genetic makeup and immune system are similar to ours. Also, they have transparent bodies, making it easy to observe biological processes under the microscope. Chris Hall (left) and co-researcher Guy Warman with the zebrafish used as a model organism in their study. Photo: Supplied / Chris Hall We focus on an immune cell called a "neutrophil", a type of white blood cell. We're interested in these cells because they specialise in killing bacteria, are first responders to infection, and are the most abundant immune cell in our bodies. Because they are very short-lived cells, neutrophils isolated from human blood are notoriously difficult to work with experimentally. However, with transparent larval zebrafish, we can film them to directly observe how these cells function, within a completely intact animal. Our initial studies showed the strength of immune response to bacterial infection peaked during the day, when the animals are active. We think this represents an evolutionary response that provides both humans and zebrafish a survival advantage. Because diurnal animals such as humans and zebrafish are most active during daylight hours, they are more likely to encounter bacterial infections. This work made us curious to know how this enhanced immune response was being synchronised with daylight. By making movies of neutrophils killing bacteria at different times of the day, we discovered they killed bacteria more efficiently during the daytime than at night. We then genetically edited neutrophils to turn off their circadian clocks by carefully removing specific clock components. This is an approach similar to removing important cogs from an analogue clock so it doesn't tick anymore. This led to the discovery that these important immune cells possess an internal light-regulated circadian clock that alerts the cells to daytime (similar to an alarm clock). This boosts their ability to kill bacteria. Our next challenge is to understand exactly how light is detected by neutrophils, and whether human neutrophils also rely on this internal timing mechanism to regulate their antibacterial activity. We're also curious to see if this killing mechanism is restricted to certain types of bacteria, such as those we're more likely to encounter during the day. Or is it a more general response to all infectious threats (including viral infections)? This research unlocks the potential for developing drugs that target the neutrophil circadian clock to regulate the cells' activity. Given neutrophils are the first and most abundant immune cells to be recruited to sites of inflammation, the discovery has very broad implications for many inflammatory conditions. * The research described here was led by PhD candidates Lucia Du and Pramuk Keerthisinghe, and was a collaboration between the Hall laboratory and the Chronobiology Research Group, led by Guy Warman and James Cheeseman, at the University of Auckland's Faculty of Medical and Health Sciences. This story was originally published on The Conversation. * Chris Hall is an Associate Professor of Immunology, University of Auckland, Waipapa Taumata Rau Sign up for Ngā Pitopito Kōrero, a daily newsletter curated by our editors and delivered straight to your inbox every weekday.
Hans India
25-05-2025
- Health
- Hans India
Daylight can boost immune system's ability to ward off infections: Study
New Delhi: A team of researchers has discovered how daylight can boost the immune system's ability to fight infections. The finding paves the way for development of drugs that target the circadian clock in neutrophils to boost their ability to fight infections, said the study led by scientists at Waipapa Taumata Rau, University of Auckland. The team focused on the most abundant immune cells in our bodies, called 'neutrophils', which are a type of white blood cell. These cells move quickly to the site of an infection and kill invading bacteria. The researchers used zebrafish, a small freshwater fish, as a model organism, because its genetic make-up is similar to ours and they can be bred to have transparent bodies, making it easy to observe biological processes in real time. 'In earlier studies, we had observed that immune responses peaked in the morning, during the fish's early active phase,' says Associate Professor Christopher Hall, from the Department of Molecular Medicine and Pathology. 'We think this represents an evolutionary response such that during daylight hours the host is more active so more likely to encounter bacterial infections,' Hall added. However, the scientists wanted to find out how the immune response was being synchronised with daylight. With this new study, published in Science Immunology, neutrophils were found to possess a circadian clock that alerted them to daytime, and boosted their ability to kill bacteria. Most of our cells have circadian clocks to tell them what time of day it is in the outside world, in order to regulate the body's activities. Light has the biggest influence on resetting these circadian clocks. 'Given that neutrophils are the first immune cells to be recruited to sites of inflammation, our discovery has very broad implications for therapeutic benefit in many inflammatory diseases,' Hall noted. Current research is now focused on understanding the specific mechanisms by which light influences the neutrophil circadian clock.
