AURORA, CO, Jan. 22, 2026 (GLOBE NEWSWIRE) -- Researchers at the University of Colorado Anschutz Linda Crnic Institute for Down Syndrome (Crnic Institute) have uncovered compelling evidence that individuals with Down syndrome experience significant alterations in liver metabolism, including elevated levels of bile acids in the bloodstream and other biomarkers of liver dysfunction. The study, published in Cell Reports, suggests that these changes may be modifiable through diet, providing hope for improved health outcomes.
Results Identify Unique Liver Dysfunction in Down Syndrome
The liver is a dynamic and vital organ that removes toxins from blood, produces bile for fat digestion, metabolizes nutrients, and makes proteins for blood clotting, making it essential for detoxification, metabolism and immunity. Using multiomic analysis of plasma samples from more than 400 research participants in the Human Trisome Project, a large cohort study of the population with Down syndrome run by the Crnic Institute, the team identified consistent elevations in bile acids across the lifespan, independent of body mass index (BMI) or co-occurring conditions. Bile acids are molecules made from cholesterol in the liver that are crucial for digesting fats and fat-soluble vitamins in the small intestine, while also acting as signaling molecules that can regulate metabolism and inflammation.
The study also demonstrated that hepatocytes, the most abundant cells in the liver, derived from induced pluripotent stem cells donated by individuals with Down syndrome exhibit intrinsic metabolic dysfunction, including altered bile acid production and abnormally high fat storage. These cellular findings reinforce the systemic observations in research participants and point to a genetic basis for liver abnormalities in Down syndrome.
To better understand the mechanisms underlying liver dysfunction in Down syndrome, Crnic Institute researchers turned to the Dp16 mouse model, which mirrors many genetic features of Down syndrome. These mice exhibited striking abnormalities in the liver, including inflammation, fibrosis, and a ductular reaction, a phenomenon involving bile duct proliferation and remodeling of blood vessels. Metabolomic analysis revealed elevated bile acids like those observed in people with Down syndrome, and gene expression profiling uncovered widespread disruptions in metabolic and inflammatory signaling pathways. Notably, dietary fat intake profoundly influenced these outcomes: mice fed a high-fat diet developed steatosis, a form of liver disease, and exacerbated liver injury, while a low-fat diet mitigated these effects.
“Our data show that Down syndrome profoundly impacts hepatic metabolism,” says Kelly Sullivan, PhD, senior author and associate professor of Pediatrics at the University of Colorado Anschutz. “Importantly, we found that dietary fat intake can exacerbate or ameliorate these effects in the mouse models, suggesting that nutrition could play a key role in managing liver health in this population.”
"The study demonstrates the importance of combining human research studies with cellular and animal models to drive scientific discovery," says Lauren Dunn, PhD, lead author of the study. "These findings open the door to practical interventions, where something as simple as dietary modification could significantly improve liver and overall health."
A Healthy Liver is Vital to Living Longer with Down Syndrome
Liver disease affects up to 100 million adults in the U.S., yet its prevalence in Down syndrome has been poorly understood. This research provides comprehensive evidence of liver dysfunction in Down syndrome and underscores the importance of early monitoring and dietary strategies to reduce risk.
“The liver is an incredibly important organ for many biological functions across the lifespan, even mild liver dysfunction can have broad impacts on human health,” says Joaquín Espinosa, PhD, executive director of the Crnic Institute and professor of Pharmacology. “The fact that liver dysfunction had not been well documented in this population until now highlights the value of transformative research funding through the National Institutes of Health INCLUDE Project and the Global Down Syndrome Foundation.”
“GLOBAL is so grateful to our donors and research participants who make this kind of breakthrough research possible,” says Michelle Sie Whitten, president & CEO of the Global Down Syndrome Foundation (GLOBAL). “Our dedicated scientists understand the importance of a healthy liver and related functions. With additional research in this area, we hope that more detailed information on diet and other treatments will help my 22-year-old daughter and millions of others with Down syndrome to live longer, healthier lives.”
The research team plans to explore clinical interventions, including low-fat diets and lifestyle modifications, to determine their impact on liver health in individuals with Down syndrome.
About the Linda Crnic Institute for Down Syndrome
The Linda Crnic Institute for Down Syndrome is one of the only academic research centers fully devoted to improving the lives of people with Down syndrome through advanced biomedical research, spanning from basic science to translational and clinical investigations. Founded through the generous support and partnership of the Global Down Syndrome Foundation, the Anna and John J. Sie Foundation, and the University of Colorado, the Crnic Institute supports a thriving Down syndrome research program involving over 50 research teams across four campuses on the Colorado Front Range. To learn more, visit www.crnicinstitute.org or follow us on Facebook, Instagram, X, Bluesky, and LinkedIn @CrnicInstitute.
About the University of Colorado Anschutz
The University of Colorado Anschutz is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado – which see more than two million adult and pediatric patient visits yearly. Innovative, interconnected and highly collaborative, CU Anschutz delivers life-changing treatments, patient care and professional training and conducts world-renowned research fueled by $910 million in annual research funding, including $757 million in sponsored awards and $153 million in philanthropic gifts.
About Global Down Syndrome Foundation
The Global Down Syndrome Foundation (GLOBAL) is the largest non-profit in the U.S. working to save lives and dramatically improve health outcomes for people with Down syndrome. GLOBAL established the first Down syndrome research institute and supports over 400 scientists and over 2,700 patients with Down syndrome from 35 states and 11 countries. Working closely with Congress and the National Institutes of Health, GLOBAL is the lead advocacy organization in the U.S. for Down syndrome research and care. GLOBAL has a membership of 130 Down syndrome organizations worldwide, and is part of a network of Affiliates – the Crnic Institute for Down Syndrome, the Sie Center for Down Syndrome, the University of Colorado Alzheimer’s and Cognition Center – all on the Anschutz Medical Campus, and the GLOBAL Adult Down Syndrome Clinic at Denver Health.
GLOBAL’s widely circulated medical publications include Global Medical Care Guidelines for Adults with Down Syndrome, Prenatal & Newborn Down Syndrome Information, and the award-winning magazine Down Syndrome World TM. GLOBAL also organizes the annual AcceptAbility Gala in Washington DC, and the annual Be Beautiful Be Yourself Fashion Show, the largest Down syndrome fundraiser in the world. Visit globaldownsyndrome.org and follow us on social media Facebook, X, Instagram, and LinkedIn.
Attachments
Anca Call Global Down Syndrome Foundation (720) 320-3832 acall@globaldownsyndrome.org Alex Lee Global Down Syndrome Foundation (720) 548-5631 alee@globaldownsyndrome.org
