Environmental Microbial Exposure, Immune Activation, and Mood Variability among Urban vs. Rural Filipino Populations

Background: The biodiversity hypothesis and the microbiota–immune–brain (MIB) axis posit that reduced environmental microbial contact in urban settings elevates inflammatory tone and worsens mood. Methods: In a cross-sectional comparison of Filipino adults (n=200; Quezon City [QC] urban=100, Nueva Ecija [NE] rural=100), we quantified standardized air/dust exposure indices (Shannon, Simpson, log10 CFU, EMDE_z), serum cytokines by ELISA (IL-1β, TNF-α; BSL-2), and mood (PHQ-9, PANAS), adjusting for age, BMI, SES quartiles, PSQI, and smoking. Analyses used Welch t tests, Pearson’s r, and OLS with HC3 errors; mediation was tested with 1,000 bias-corrected bootstraps. Results: Microbial diversity was lower in QC than NE (Shannon M=2.59 vs 3.27; t=−14.30, p<.001; g=−2.01), while pro-inflammatory cytokines were higher in QC (lnIL-1β M=1.438 vs 0.793, t=10.87, p<.001, g=1.53; lnTNF-α M=1.933 vs 1.389, t=11.27, p<.001, g=1.59). Diversity inversely correlated with inflammation (e.g., Shannon–lnIL-1β r=−0.719; Shannon–lnTNF-α r=−0.665; all p<.001), and inflammation tracked mood (lnTNF-α with PHQ-9 r=0.776; with PANAS-NA r=0.785; with PANAS-PA r=−0.487; all p<.001). In mediation, Shannon predicted lower lnTNF-α (a=−0.512, p<.001), which predicted higher PHQ-9 (b=4.618, p<.001); the indirect effect was significant (a×b=−2.366, 95% CI −2.945 to −1.800), with a residual direct effect (c′=−0.516, p<.001). Conclusions: Higher environmental microbial diversity is associated with dampened inflammatory activity and lower depressive burden, supporting a bio-ecological pathway linking urbanicity, immunity, and affect. Findings suggest biodiversity-aware urban design as a mental-health–relevant policy lever.