Multi-trajectories of body mass index, waist circumference, gut microbiota, and incident dyslipidemia: a 27-year prospective study.

Background:Evidence is insufficient to establish a longitudinal association between combined trajectories of body mass index (BMI) and waist circumference (WC) and dyslipidemia. Our study aimed to explore the association between multi-trajectories of BMI and WC and incident dyslipidemia and identify microbiota and metabolite signatures of these trajectories. Methods:Stratified by sex, we used a group-based trajectory modeling approach to identify distinct multi-trajectories of BMI and WC among 10,678 participants from the China Health and Nutrition Survey over a 24-year period. For each sex, we examined the associations between these multi-trajectories (1991-2015) and the onset dyslipidemia (2018) using multivariable logistic regression adjusting for sociodemographic and lifestyles factors. We characterized the gut microbial composition and performed LASSO and logistic regression to identify gut microbial signatures associated with these multi-trajectories in males and females, respectively. Results:We identified four multi-trajectories of BMI and WC among both males and females: Normal (Group 1), BMI&WC normal increasing (Group 2), BMI&WC overweight increasing (Group 3), and BMI&WC obesity increasing (Group 4). Among males, Group 2 (OR: 2.10, 95% CI: 1.28-3.46), Group 3 (OR: 2.69, 95% CI: 1.56-4.63) and Group 4 (OR: 3.56, 95% CI: 1.85-6.83) had higher odds of developing dyslipidemia. However, among females, only those in Group 2 (OR: 1.54, 95% CI: 1.03-2.30) were more likely to develop dyslipidemia. In males, compared with Group 1, we observed lower alpha-diversity within Groups 2,3, and 4, and significant beta-diversity differences within Groups 3 and 4 (p 0.001). We also identified 3, 8, and 4 characteristic bacterial genera in male Groups 2, 3 and 4, and 2 genera in female Group 2. A total of 23, 25 and 10 differential metabolites were significantly associated with the above genera, except for Group 2 in males. Conclusions:The ascending combined trajectories of BMI and WC are associated with a higher risk of dyslipidemia, even with normal baseline levels, especially in males. Shared and unique gut microbial and metabolic signatures among these high-risk trajectories could enhance our understanding of the mechanisms connecting obesity to dyslipidemia.