Multi-organ metabolic dysregulation and cecal microbiota alterations following black carbon exposure

Abstract

Background

Black carbon (BC) has been linked to adverse health outcomes, yet underlying mechanisms remain unclear. Integrating metabolomic and metagenomic data across tissues may clarify BC-induced biological pathways.

Methods

We performed human epidemiology and mice experimental approaches. We included 248,288 participants with annual BC exposure estimates and plasma metabolomic profiles. Elastic net regression identified BC-associated metabolites. Male C57BL/6J mice were exposed to filtered air or BC (1 mg/m³, 1 h/day, 5 days/week, 12 weeks). Multi-tissue metabolomics and cecal contents microbiota sequencing were conducted, with histology and gene expression measurements.

Results

In humans, long-term BC exposure significantly altered plasma metabolites, notably increasing saturated fatty acids (β = 0.048), while decreasing docosahexaenoic acid (β = −0.002). Amino acid metabolism was broadly disrupted, involving elevated valine (β = 0.011) and reduced glutamine (β = −0.006). In mice, metabolomic profiling showed organ-specific shifts, including increased glutathione and cortisol in the liver (2.88-fold and 2.06-fold), increased PC(16:0/18:1(9Z)) in the heart (3.22-fold), elevated anandamide and arachidonic acid in the kidney (2.35-fold and 1.48-fold), and decreased multiple fatty acids and lysophospholipids across organs. Cecal microbiota exhibited reduced alpha-diversity (Shannon: 3.67 vs. 4.50, P < 0.05) and taxonomic shifts, including an increased abundance of g_Akkermansia and decrease in g_Bacteroides. Multi-omics integration revealed significant microbiota-metabolome correlations in the cecum and plasma (Mantel r = 0.276, P = 0.012). Histological examination confirmed organ injuries, notably lung inflammation, cardiac edema, and neuronal condensation. Gene expression analysis showed increased Il-6 in the lung (5.35-fold, P = 0.047), increased Mb in the heart (5.18-fold, P = 0.010), and increased Igfbp7 in the kidney (3.03-fold, P = 0.001), while Tjp1 expression in cecum was reduced (0.42-fold, P = 0.004).

Conclusions

Our findings suggest that BC exposure may alter systemic metabolism and gut microbiota, potentially contributing to tissue injury and inflammation. The gut–organ axis could be a target for mitigating BC-related health effects.