Association between physical activity level and gut microbiota profiles in individuals with subthreshold depression:...

Subthreshold depression (SD) represents a subclinical state between mental health and major depressive disorder (MDD) and is associated with a high prevalence and substantial risk of progression to MDD. Physical activity (PA) has been proposed to exert antidepressant effects through modulation of the gut-brain axis. However, the association between PA level and gut microbiota profiles in individuals with SD remains poorly understood.

This is a cross-sectional observational study. Stratified random sampling was used to screen full-time undergraduates aged 18-25 years at Jimei University for subthreshold depression. Following initial screening with the CES-D and secondary screening with a structured clinical interview, the HAMD-17, and the BDI-II, 122 participants were enrolled. Participants were assigned by IPAQ short form to low (n = 46), moderate (n = 47), and high (n = 29) physical activity groups. Cardiorespiratory fitness was assessed as maximal oxygen uptake estimated by a submaximal Astrand-Rhyming cycle ergometer test. Fecal samples were subjected to 16S rRNA gene V3-V4 sequencing; α-diversity, β-diversity, differential genera, and keystone species were analyzed.

No significant differences in α-diversity or β-diversity were observed among the three PA groups (P > 0.05). However, distinct taxonomic signatures were identified. The low-PA group was enriched in potentially pro-inflammatory taxa, including Streptococcaceae and Eggerthella (P < 0.05), whereas the moderate-PA group exhibited increased abundance of butyrate-producing genera, including Roseburia and Lachnospiraceae_UCG-010 (P < 0.05). The high-PA group showed significant enrichment of Dorea (P < 0.05). Faecalibacterium exhibited the highest Structural Keystoneness (Ks) within the microbial co-occurrence network, and its relative abundance was positively associated with VO₂max. Moreover, Median (Ks) was strongly correlated with MAD (Ks) (ρ = 0.602, P < 0.001), indicating that the ecological importance of high-keystone taxa is highly context dependent.

Although PA level was not significantly associated with overall gut microbial diversity in college students with SD, it was closely associated with the differential distribution of specific functional genera. These findings provide novel evidence supporting the role of PA-related microbial remodeling in SD and may facilitate the development of microbiota-targeted interventions that mimic exercise-induced benefits.