bstract Aims Brain disease, in its many forms, has recently demonstrated a great socio-economic impact and represents one of the hardest challenges of present research. Although each pathology of this highly heterogenous group is characterized by individual features, there is an increasing number of common toxicological mechanisms that have been evidenced. This review aims to summarize the state-of-art knowledge concerning the role of environmental bacteria in brain diseases focusing on different mechanisms of action that could be interacting in an additive or synergistic way. Materials and methods For this wide-range subject, we focused on two emerging types of bacterial-derived brain exposure and damage and specifically treated representative examples: i) environmental bacterial-derived compounds in the form of the cyanobacterial product BMAA (β-N-methylamino-L-alanine) toxin and its isomers DAB (2,4-diaminobutyric acid) and AEG (N-(2-aminoethyl)glycine) and ii) toxicity related to bacterial infections in the form of the emerging Lyme neuroborreliosis (LNB), determined by Borrelia burgdorferi (Bb). Key findings Defined as pleiotropic contaminants, BMAA and Bb act through multiple toxicological pathways including inflammation, oxidative stress and excitotoxicity. Multiple investigations in in vitro and in vivo models have underlined the involved mechanisms of action but further investigations are needed to clarify the role of possible cocktail effects and underline possible new targets of intervention. Significance Environmental bacteria represent emerging risk factors because of environmental changes, anthropogenic activities and human lifestyle evolutions. Future directions and research ambitions are here discussed in order to evaluate human risk and possible ways of intervention and prevention.