While GDNF plays a role in neuroprotection and neuroplasticity in the central and peripheral nervous system, other factors such as BDNF, ciliary neurotrophic factor, NGF, or neurotrophin-3 can directly impact protective barrier–environment interactions along the gut–brain axis, influencing cognition and behaviors related to anxiety and depression during stress exposure (Liu, 2018; Lapmanee et al., 2017, 2023a). This evidence concerns the gene CNTF and major depressive disorder.