Multi-Omics Exploration of Obesity Biomarkers in Sedentary and Weight Loss Cohorts

Sedentary behavior for two years during the coronavirus disease 2019 (COVID-19) pandemic contributes to weight gain. Gut microbiota and blood metabolome are related to body mass index (BMI) and indicate individual metabolic changes. Surgery and exercise are effective weight-loss methods. The precise plasma metabolites and gut microbiota biomarkers involved and the underlying mechanisms are still largely unclear. To address this issue, we analyzed weight gain and weight loss cohorts to identify biomarkers associated with obesity. In the sedentary cohort, 49 subjects were recruited in year 2019. After two years of sedentary behavior during the COVID-19 pandemic, the BMI of 24 subjects significantly increased (Weight gain group), while that of the remnant 25 subjects remained constant (Maintaining weight group). At baseline and two years post baseline, the gut microbiota and blood metabolome, as well as body composition and clinical indicators, were all collected. In weight loss studies, we analyze the plasma metabolome of the two cohorts, including individuals who underwent laparoscopic sleeve gastrectomy (LSG) surgery and exercise intervention. Weight gain through sedentary behavior contributed to the variation of the gut microbiota and plasma metabolites composition. Creatine, phenylalanine and tyrosine exhibited significant positive associations with BMI and fat mass. We further confirmed the association between BMI and plasma metabolites in two weight loss cohorts. By utilizing a linear regression model, we found that 10 metabolites including creatine were correlated with BMI in weight loss individuals. Based on receiver operating characteristic (ROC) curves, creatine exhibited a satisfactory classification performance in regard to predicting weight reduction (AUC_LSG = 0.890, AUC_{S ports} = 0.840). Moreover, some gut microbiota, including Bifidobacterium angulatum DSM 20098 = JCM 7096 and Rothia dentocariosa M567I could affect BMI through the mediating factor of creatine.

The online version contains supplementary material available at 10.1007/s43657-024-00165-x.