Fig. 1

Schematic representation of the “triple-hit” hypothesis. The initial brain injury sets off sympathetic hyperactivity and catecholamine storm, a well-established contributor to ALI. Furthermore, the direct consequences of ABI, characterized by inflammation and oxidative stress (termed the “first hit”), render the lungs susceptible to subsequent interventions like MV, infections, and surgery (referred to as the “second hit”). Notably, the pivotal role of the gut–lung axis in respiratory health reveals that dysbiosis and intestinal dysfunction in ABI patients initiate a sequence of events involving immune dysregulation and microbiome alterations, which subsequently impact the lung tissue. This activation of the gut–lung axis constitutes the “third hit,” culminating in the onset or exacerbation of ALI. ABI: Acute brain injury; ALI: Acute lung injury; ARDS: Acute respiratory distress syndrome; CAP: Cholinergic anti-inflammatory pathway; E/NE: Epinephrine/norepinephrine; HPA: Hypothalamic–pituitary–adrenal; MV: Mechanical ventilation