The regulatory role of gut microbiota in energy metabolism disorders of distal organs by emerging contaminants

Emerging contaminants (ECs) are a significant category of newly recognized pollutants with potential risks to human health. Human are exposed to ECs via several ways including air, food, and water. The gut microbiota (GM) and its metabolites can be closely linked to multi-organ energy metabolism in the body. Despite substantial studies on the health impacts induced by ECs, a comprehensive understanding of the pathways through which ECs influence gut-target organ energy metabolism remains absent. This study demonstrates that ECs disrupt GM balance, which subsequently triggers systemic inflammation through the nuclear factor kappa-B (NF-κB)/janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways, induces insulin resistance (IR) by inhibiting insulin receptor substrate 1 (IRS1) phosphorylation, and impairs bile acid (BA) metabolism via farnesoid X receptor (FXR) signaling dysregulation. Ultimately, these mechanisms lead to abnormal energy metabolism in multiple organs including the liver, brain, and reproductive system. In addition, probiotics hold promising application potential in alleviating the harmful metabolic effects induced by ECs. By modulating the composition of the GM, enhancing intestinal barrier function, reducing inflammation, and producing metabolic products, probiotics are expected to restore metabolic homeostasis in distant organs. Therefore, this review explores the potential interactions between ECs and the energy metabolism of gut-target organs. It summarizes the detrimental effects of ECs-induced GM, consolidates possible mechanistic pathways linking GM disruption to abnormal energy metabolism, discusses probiotics as potential interventions to support preventive strategies, and suggests that Future research should focus on developing personalized and combined probiotic intervention strategies, and further elucidate their mechanisms of action, in order to fully exploit the health-protective potential of probiotics.