: Over the last years, research has focused on microbiota to establish a missing link between
neuronal health and intestine imbalance. Many studies have considered microbiota as critical
regulators of the gut–brain axis. The crosstalk between microbiota and the central nervous system is
mainly explained through three different pathways: the neural, endocrine, and immune pathways,
intricately interconnected with each other. In day-to-day life, human beings are exposed to a wide
variety of contaminants that affect our intestinal microbiota and alter the bidirectional communication
between the gut and brain, causing neuronal disorders. The interplay between xenobiotics, microbiota
and neurotoxicity is still not fully explored, especially for susceptible populations such as pregnant
women, neonates, and developing children. Precisely, early exposure to contaminants can trigger
neurodevelopmental toxicity and long-term diseases. There is growing but limited research on the
specific mechanisms of the microbiota–gut–brain axis (MGBA), making it challenging to understand
the effect of environmental pollutants. In this review, we discuss the biological interplay between
microbiota–gut–brain and analyse the role of endocrine-disrupting chemicals: Bisphenol A (BPA),
Chlorpyrifos (CPF), Diethylhexyl phthalate (DEHP), and Per- and polyfluoroalkyl substances (PFAS)
in MGBA perturbations and subsequent neurotoxicity. The complexity of the MGBA and the changing
nature of the gut microbiota pose significant challenges for future research. However, emerging insilico models able to analyse and interpret meta-omics data are a promising option for understanding
the processes in this axis and can help prevent neurotoxicity. CLICK TO REVIEW
Keywords: in-vivo; in-silico; neurotoxicity; gut microbiota; BPA; DEHP; Chlorpyrifos; PFAS