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. 2019 Nov 6;10:1155. doi: 10.3389/fneur.2019.01155

Figure 4.

Figure 4

Potential mechanism of probiotic treatment in PD. The GM impacts PD via three primary modalities (neuronal mechanism, endocrine mechanism, and immunological mechanism). [1] The GM can both produce and stimulate certain neurotransmitters via/or not via secretory ECs. ECs can also produce certain neuroactive factors, such as PYY, Trp, and His. These two types of components cross into the BBB and impact the CNS. Some gut hormones stimulated by neuroactive components, like ghrelin and IPA, can have dual effects on the CNS. The GM can directly trigger electrical signals in the ENS through the vagus nerve to the DMV. Finally, the GM may release glucose through SCFAs and FFA to propagate signals through the ENS. [2] The GM can directly and indirectly affect a battery of endocrine signaling components. SCFAs, as the main microbial metabolites, are major signaling molecules that may activate several pathways, as shown in the figure. HPA axis stimulation and the release of endocrine components are also triggered by the GM. Those endocrine components, including cortisol, and ferulic acid, have multiple roles in several pathways in PD. [3] Specific GM members could suppress both chronic and pathological inflammation. Microbe-associated molecular patterns on the surface of GM members directly activate receptors on immune cells like DCs and upregulate/suppress inflammatory cytokines. Finally, the GM influences the production of mucin through the gut. AC, acetylcholine; BBB, blood–brain barrier; CNS, central nervous system; CRMP2, collapsin response mediator protein family; DA, dopamine; DHA, docosahexaenoic acid; DMV, dorsal motor nucleus of the vagus; EC, enterochromaffin cell; ENS, enteric nervous system; EPA, eicosapentaenoic acid; FFAR, free fatty acid receptors; GABA, gamma aminobutyric acid; GM, gut microbiota; His, histamine; HPA axis, hypothalamic–pituitary–adrenal axis; IFNγ, interferon gamma; IL-10, interleukin 10; IL-12, interleukin 12; IPA, indole-3-propionic acid; PYY, peptide YY; ROS, reactive oxygen species; SCFAs, short-chain fatty acids; TNFα, tumor necrosis factor alpha; Trp, tryptophan; 5HT, serotonin.