Mechanisms of disruption of the gut–brain axis by environmental endocrine disruptors

Abstract

Environmental endocrine disruptors (EEDs) are exogenous chemicals that impair physiological health by disrupting endocrine function. The gut–brain axis represents a complex bidirectional communication network integrating the gut microbiome, immune system, neural signaling, and endocrine pathways to maintain systemic homeostasis. Within this interconnected system, gut microbiota influence mood regulation, immune activity modulates neural processes, and neural signaling governs circadian and sleep cycles. This review explores the multi-system impacts of EEDs across four key physiological domains: (1) gut microbial ecology, (2) immune function, (3) neuroendocrine regulation, and (4) developmental processes. Evidence indicates that EED exposure disrupts intestinal microbial composition, leading to dysbiosis marked by the depletion of beneficial taxa and the expansion of pathogenic species. Concurrently, EEDs impair gut-associated immune cell populations (T cells, B cells, and macrophages), undermining mucosal immunity and increasing susceptibility to inflammatory bowel disease, autoimmune conditions, and gastrointestinal malignancies. At the endocrine level, EEDs interfere with the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes, contributing to hormonal imbalances and impaired reproductive development. Neurochemically, they disrupt the synthesis, release, and degradation of key neurotransmitters, including norepinephrine, dopamine, and serotonin, while exerting direct neurotoxic effects such as cerebrovascular abnormalities and delayed cerebellar myelination. In summary, this review delineates the mechanistic pathways through which EEDs perturb gut–brain axis homeostasis. These insights provide a scientific basis for designing targeted therapeutic interventions and shaping evidence-based public health policies.