New blood-based biomarkers could help predict bariatric surgery outcomes in teens

A USC-led team has developed an innovative way to predict blood pressure outcomes after bariatric surgery that outperforms the current standard practice. In 108 adolescents who underwent bariatric surgery, the researchers used blood tests taken before the procedure to predict which patients would have improved blood pressure five years later. The study is one of the first to use cutting-edge “omics” techniques, which analyze the body’s small molecules and proteins, to predict long-term health outcomes.

“High blood pressure in adolescence can set the stage for lifelong heart disease, yet we still know little about why some young people respond better to treatment than others,” said the study’s senior author, Vaia Lida Chatzi, MD, PhD, a professor of population and public health sciences and pediatrics and director of the Center for Translational Exposomics Research (CTER) at the Keck School of Medicine of USC.

Using a combination of metabolomics and proteomics, which analyze thousands of small molecules and proteins in the body to give a snapshot of cellular function, researchers identified the top 10 molecules linked to improved blood pressure five years after surgery. These 10 molecules gave better predictions of which patients would improve than the current predictive approach, which uses a combination of demographic factors and clinical tests.

Five of the 10 molecules were also linked to blood pressure in another group of youth with above average BMI, suggesting the findings may be broadly applicable. The results were just published in the journal Hypertension. 

“This is the first time blood-based biomarkers have been identified that predict which adolescents are most likely to experience improvements in blood pressure after bariatric surgery,” said Thomas H. Inge, MD, PhD, surgeon-in-chief at Ann & Robert H. Lurie Children’s Hospital of Chicago and professor of surgery at Northwestern University Feinberg School of Medicine, co-author and principal investigator of the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study, which includes the teens who participated in this research.

The findings represent an important step in precision medicine, strengthening the case that omics can be used as predictive biomarkers. Compared to standard blood biomarkers, this approach could offer a more sensitive way to predict future health, including who will respond well to bariatric surgery.

“If we can predict outcomes before surgery, we can consider alternative treatment plans for those unlikely to benefit,” said the study’s first author, Shudi Pan, a doctoral student in epidemiology at the Keck School of Medicine. “This opens the door to more personalized, effective approaches to managing hypertension early in life.”

A better predictor of blood pressure

The researchers analyzed blood samples, taken just before bariatric surgery, from 108 adolescents in the Teen-LABS study. Using advanced metabolomics and proteomics approaches, they measured the levels of thousands of small molecules and proteins circulating in the blood.

Five years after surgery, patients returned for follow-up appointments, where their blood pressure levels were measured to check for improvements.

Using a machine learning algorithm, the researchers found 10 molecules in the pre-surgery blood samples that were linked to changes in blood pressure five years later. They then compared how well this omics data predicted outcomes against traditional risk factors—including sex, race, socioeconomic status and pre-surgery body mass index and blood pressure. The omics-based model was a better predictor of blood pressure improvements than the traditional approach.

To see if the biomarkers could be useful beyond bariatric surgery, the researchers also tested them among 79 young adults, aged 17 to 24, in the Metabolic and Asthma Incidence Research (Meta-AIR) study. These participants had higher than average BMI but had not undergone bariatric surgery. The team found five small molecules and three proteins that were linked to blood pressure levels in both studies.

“Because we saw a consistent association, we think these molecules may have a broader significance for long-term blood pressure improvement,” Pan said.

Long-term surgery outcomes

Omics studies are common in environmental exposures research, a main focus of CTER, but few research teams have explored their potential to predict long-term health outcomes. The latest advance stemmed from an ongoing collaboration between CTER’s epidemiologists and the physician scientists at Lurie Children’s.

“These data highlight the importance of trans-disciplinary collaboration. Without the multi-year partnership between the Teen-LABS study group and USC Center for Translational Research on Environmental Health, none of this work would have been possible,” said co-author Justin Ryder, PhD, vice chair of research for the Department of Surgery at Lurie Children’s and associate professor of surgery and pediatrics at Northwestern University Feinberg School of Medicine.

Next, the team will explore whether omics can predict other outcomes after bariatric surgery, such as improvements in diabetes and kidney function. They are also studying how chemical exposures, including per- and polyfluoroalkyl substances (PFAS), may affect long-term results, with the goal of developing a holistic model for identifying the best candidates for the procedure.

About this research

In addition to Chatzi, Inge, Pan and Ryder, the study’s other authors are Zhenjiang Li, Juan Pablo Lewinger, Jesse Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Max Aung, Erika Garcia, Rob McConnell, Sandrah Eckel, Zhanghua Chen, Frank Gilliland and David Conti from the Keck School of Medicine of USC, University of Southern California; Todd Jenkins from the Cincinnati Children’s Hospital Medical Center; Stephanie Sisley from Baylor College of Medicine; Stephen Daniels from the University of Colorado School of Medicine; Douglas Walker from the Emory University Rollins School of Public Health; Michele La Merrill from the University of California, Davis; and Tanya Alderete from the Johns Hopkins Bloomberg School of Public Health.

This work was supported by the National Institute of Environmental Health Sciences [R01ES030364]; the American Heart Association Predoctoral Fellowship [24PRE1187910]; and the National Institutes of Health [U01HG013288, R01ES030691, R01ES03069, R01ES029944 and P30ES007048]. The Teen-LABS consortium is supported by cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases through grants for a clinical coordinating center [UM1DK072493] and the data coordinating center [UM1DK095710].