Physical Activity, Gut Microbiota, and the Risk of Dyslipidemia in a Community-Based Cohort Study.

Background: Whether moderate-to-vigorous physical activity (MVPA) mitigates the detrimental association between sedentary behavior and dyslipidemia remains unclear, as does the link between MVPA and gut microbiota.

Methods: We prospectively evaluated the joint association between MVPA and sedentary time on dyslipidemia risk in a cohort of 2942 Chinese adults, where PA was measured by a validated self-reported questionnaire. In a subcohort (n=754), 1-year gut microbial changes associated with MVPA were assessed via fecal samples collected twice at 1-year intervals for 16S ribosomal RNA sequencing, with PA intensively assessed by 4 quarterly 3-day PA diaries (2 weekdays and 1 weekend day) during the year.

Results: From 2020 to 2025, 306 dyslipidemia were newly diagnosed. Prolonged sedentary hours increased dyslipidemia risk by 63% (highest versus lowest tertile: adjusted hazard ratio [HR], 1.63 [95% CI, 1.19-2.22], P_trend=0.002). Compared with participants with long sedentary hours and low MVPA levels (ie, long-low group), HRs of dyslipidemia for those in short-high, short-low, and long-high groups were 0.70 (95% CI, 0.50-0.98), 0.99 (95% CI, 0.71-1.37), and 0.83 (95% CI, 0.60-1.16), respectively. The microbial α-diversity declined in the low MVPA group (P=0.024), and β-diversity shifted in both low/high MVPA groups (all P≤0.005). We identified 7 MVPA-associated and 13 sedentary time-associated genera (all P_{FALSE DISCOVERY RATE}<0.05). Among these genera, Eggerthella and Desulfovibrio correlated positively with MVPA levels but inversely with sedentary time, and Desulfovibrio was inversely associated with dyslipidemia (odds ratio, 0.78 [95% CI, 0.606-0.997]).

Conclusions: MVPA attenuates the positive association between sedentary time and dyslipidemia risk and modulates gut microbial diversity and richness, suggesting microbiota-mediated pathways for dyslipidemia prevention.