The global incidence of inflammatory bowel disease (IBD) continues to rise, with environmental pollutant exposure recognized as a significant contributing factor. The gastrointestinal tract serves as a primary interface for xenobiotics, where complex interactions between the gut microbiota and host metabolism maintain intestinal homeostasis. Disruption of this delicate balance is a key event in the pathogenesis of chronic inflammatory disorders.

The novel brominated flame retardant bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), widely used as an alternative to legacy compounds, is increasingly detected in various environmental matrices and human tissues. This pervasive environmental presence has raised concerns about its potential impact on human health, particularly regarding gastrointestinal function, though the underlying mechanisms remain poorly understood.

Recently, a research group led by Prof. ZHOU Bingsheng from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences illustrated the novel molecular mechanisms associated with pollutant-induced intestinal injury, revealing how TBPH drives IBD-like pathology by disrupting the gut microbiota-arachidonic acid metabolic axis. This study was published in Environmental Science & Technology.

In this study, the researchers first established a mouse model exposed to environmentally relevant and higher doses of TBPH. They observed typical IBD-like pathological features, including colon shortening, damage to the epithelial barrier, reduced goblet cells, and elevated systemic levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. This confirmed the detrimental effects of TBPH on intestinal integrity and systemic inflammation.

Subsequently, using shotgun metagenomic sequencing, the team discovered that TBPH exposure significantly reshaped the gut microbial community. A marked depletion of the beneficial mucin-degrading bacterium Akkermansia muciniphila (AKK) was identified as a key taxonomic shift. This dysbiosis was accompanied by a significant decrease in microbial diversity and functional alterations.

Integrating untargeted metabolomics, the researchers found that TBPH exposure caused a profound disturbance in host lipid metabolism. Specifically, they observed a significant accumulation of arachidonic acid (AA) in the serum and colon tissue, alongside a decrease in its phospholipid precursors. Correlation analysis revealed a strong negative association between AA levels and AKK abundance.

Further targeted biochemical and molecular analyses elucidated the downstream inflammatory cascade. The accumulated AA led to hyperactivation of the phospholipase A2 (PLA2)–cyclooxygenase-2 (COX2)–prostaglandin E2 (PGE2) axis, resulting in excessive PGE2 production. This subsequently activated the NF-κB signaling pathway, a master regulator of inflammation, thereby amplifying the production of pro-inflammatory cytokines and exacerbating intestinal barrier damage.

To establish causality, the team conducted an intervention experiment by supplementing TBPH-exposed mice with viable A. muciniphila. This supplementation effectively restored AA metabolic homeostasis, suppressed the overactivated PLA2–COX2–PGE2–NF-κB inflammatory cascade, and mitigated intestinal barrier damage and inflammation, demonstrating the protective role of AKK.

This study demonstrates that the environmental pollutant TBPH promotes intestinal inflammation by depleting A. muciniphila, a key commensal bacterium. This depletion disrupts arachidonic acid metabolic homeostasis, leading to the over-activation of a pro-inflammatory signaling axis. The findings highlight the critical role of the gut microbiota-metabolite interface in chemical-induced toxicity and provide a scientific basis for environmental health risk assessment of emerging pollutants. Furthermore, they suggest the potential of microbiome-targeted strategies, such as probiotic intervention, in preventing or alleviating pollutant-associated intestinal disorders.

(Editor: MA Yun)