Glycomic biomarkers are instrumental for suboptimal health status management in the context of predictive, preventive, and personalized medicine.

Objectives: Suboptimal health status (SHS), a reversible borderline condition between optimal health status and disease, has been recognized as a main risk factor for non-communicable diseases (NCDs). From the standpoint of predictive, preventive, and personalized medicine (PPPM/3PM), the early detection of SHS provides a window of opportunity for targeted prevention and personalized treatment of NCDs. Considering that immunoglobulin G (IgG) N-glycosylation levels are associated with NCDs, it can be speculated that IgG N-glycomic alteration might occur at the SHS stage. Methods: A case-control study was performed and it consisted of 124 SHS individuals and 124 age-, gender-, and body mass index-matched healthy controls. The IgG N-glycan profiles of 248 plasma samples were analyzed by ultra-performance liquid chromatography instrument. Results: After adjustment for potential confounders (i.e., age, levels of education, physical activity, family income, depression score, fasting plasma glucose, and low-density lipoprotein cholesterol), SHS was significantly associated with 16 IgG N-glycan traits at 5% false discovery rate, reflecting decreased galactosylation and fucosylation with bisecting GlcNAc, as well as increased agalactosylation and fucosylation without bisecting GlcNAc. Canonical correlation analysis showed that glycan peak (GP) 20, GP9, and GP12 tended to be significantly associated with the 5 domains (fatigue, the cardiovascular system, the digestive system, the immune system, and mental status) of SHS. The logistic regression model including IgG N-glycans was of moderate performance in tenfold cross-validation, achieving an average area under the receiver operating characteristic curves of 0.703 (95% confidence interval: 0.637-0.768). Conclusions: The present findings indicated that SHS-related alteration of IgG N-glycans could be identified at the early onset of SHS, suggesting that IgG N-glycan profiles might be potential biomarker of SHS. The altered SHS-related IgG N-glycans are instrumental for SHS management, which could provide a window opportunity for PPPM in advanced treatment of NCDs and shed light on future studies investigating the pathogenesis of progression from SHS to NCDs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00278-1.