Potential role of the brain-gut-microbiota axis in ALS. There is a two-way interaction between the brain-gut-microbiota axis. It acts in many ways, including immune, nervous, and endocrine mechanisms. In the immune mechanism, the gut microbiota can affect the CNS through two links of peripheral inflammation and central inflammation, in which LPS plays an important role. LPS can activate monocytes and macrophages in peripheral blood to induce the release of a large number of pro-inflammatory cytokines. In addition, TNF-α and IL-10 also play an important role in the immune mechanism. In the neural mechanism, gut microbiota signals can communicate bidirectionally with the CNS through ANS and ENS, and the mainly functional parts include vagus nerve, Paneth cell, and ENS. As for endocrine mechanism, small molecular substances from various bacteria, including SCFAs, NAM, NA, NR and others, play an important role in the development of ALS disease. They can enter the circulatory system through the blood and affect CNS. Any abnormality in any part of any one mechanism may cause the disorder of the whole brain-gut-microbiota axial circuit.