Associations Between Serum Gut-Derived Tryptophan Metabolites and Cardiovascular Health Markers in Adoles-cents with Obesity

Authors: RIVERA, JENY - University Arkansas For Medical Sciences (UAMS); LAN, RENNY - University Arkansas For Medical Sciences (UAMS); FERRUZZI, MARIO - University Arkansas For Medical Sciences (UAMS); BØRSHEIM, ELISABET - University Arkansas For Medical Sciences (UAMS); TAS, EMIR - University Of Pittsburgh School Of Medicine; DIAZ, EVA - University Arkansas For Medical Sciences (UAMS)

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/22/2025
Publication Date: 7/25/2025
Citation: Rivera, J.E., Lan, R., Ferruzzi, M.G., Børsheim, E., Tas, E., Diaz, E.C. 2025. Associations Between Serum Gut-Derived Tryptophan Metabolites and Cardiovascular Health Markers in Adoles-cents with Obesity. Nutrients. 17(15): article 2430. https://doi.org/10.3390/nu17152430.
DOI: https://doi.org/10.3390/nu17152430

Interpretive Summary: Background: Tryptophan is a nutrient found in foods like turkey, eggs, and cheese. When tryptophan is broken down in the gut, it produces special substances called tryptophan metabolites. In animal studies, these substances have been linked to protection against heart disease and problems with metabolism. However, little is known about how these substances affect adolescents with obesity. Methods:Blood samples were collected at the Arkansas Children's Nutrition Center from 28 adolescents between the ages of 13 and 18 who had obesity. The levels of different tryptophan-related substances in the blood were measured. These levels were compared with health markers such as body weight, fitness level, blood pressure, cholesterol, and blood sugar. Results: Lower levels of indole-3-propionic acid and indole were found in teens with higher levels of obesity. Indoxyl sulfate, indole-acrylic acid, and indole-3-lactic acid were found in higher amounts in boys compared to girls. Higher levels of indole-3-propionic acid were linked to lower diastolic blood pressure and lower LDL cholesterol (the “bad” kind), even after body weight was considered. Higher indoxyl sulfate levels were linked to higher blood sugar, regardless of sex. Teens who identified as Hispanic had higher levels of indole and indole-3-acetic acid compared to other ethnic groups. Conclusions: The levels of certain gut-related tryptophan metabolites were shown to be related to markers of heart and metabolic health in teenagers with obesity. These early findings suggest that changes in these substances may play a role in blood pressure, cholesterol, and blood sugar control. Further studies are needed to better understand how these substances affect health trajectories of adolescents.

Technical Abstract: Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulat-ing gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m2). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO2 peak) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: In-dole-3-propionic acid was inversely associated with diastolic blood pressure (rho = -0.39, p = 0.047), total cholesterol (rho = -0.55, p = 0.002), and LDL-C (rho = -0.57, p = 0.0014), in-dependent of sex and obesity severity. Indoxyl sulfate was positively correlated with fast-ing glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = -0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No sig-nificant associations were observed between Trp metabolites and FMD, VO2 peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk.