Table 1.
Overview of the complex roles of amino acids in the microbiome-gut-immune-brain axis in ASD.
| AA | Body fluid levels in ASD | Effects on the microbiota | Effects on the intestines | Effects on the immune system | Effects on mTOR | Effects in the brain | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Leu | ↓ Blood, urine, CSF (126) | ↓ Proteobacteria (194) | ↓ F/B (194) | ↓ MC activation (93) | ↓ Inflammatory response mϕ (95) | Essential for lymphocyte proliferation (97, 98) | Essential for Ig production (100) | ↑ MC and EC (92) | ↑ Microglia phagocytosis (107) | ↓ Neuro-protective factor microglia (107) | ||
| Ile | ↓ Blood, urine, CSF (126) | ↓ Proteobacteria (194) | ↓ F/B (194) | ↓ MC activation (93) | ↓ Inflammatory response mϕ (95) | Essential for lymphocyte proliferation (97, 98) | Essential for Ig production (100) | ↑ MC and EC (92) | ↑ Microglia phagocytosis (107) | ↓ Neuro-protective factor microglia (107) | ||
| Val | ↓ Blood, urine, CSF (126) | ↓ Proteobacteria (194) | ↓ F/B (194) | ↓ MC activation (93) | ↓ Inflammatory response mϕ (95) | Essential for lymphocyte proliferation (97, 98) | Essential for Ig production (100) | ↑ MC and EC (92) | ↑ Microglia phagocytosis (107) | ↓ Neuro-protective factor microglia (107) | ||
| His | ↑ Blood (126) ↓ Urine (126) | ↓ Inflammatory response EC (115) | ↓ MC activation (93) | ↓ Th2 and Th17 cells (93) | ↑ Treg cells (93) | ↓ Inflammatory response mϕ (116) and PBMC (114, 115) | ↓ Brain, MC and EC (92) | |||||
| Thr | ↓ Blood (126) | Fermented into SCFA (163, 174) | ↑ Epithelial barrier (109) | ↑ Mucus production (110, 111) | ↓ MC activation (93) | ↓ Th2 and Th17 cells (93) | ↑ Treg cells (93) | ↓ Brain, MC and EC (92) | ||||
| Lys | ↑ Blood, Urine (126) | ↓ MC activation (93) | ↓ Th2 and Th17 cells (93) | ↑ Treg cells (93) | Essential for downregulating inflammatory cytokines and NO production (117) | ↓ Brain, MC and EC (92) | ||||||
| Gly | - (126) | Protects EC (118) | ↓ Intestinal inflammation (120–122) | ↓ Inflammatory response mϕ (119) | ||||||||
| Gln | ↓ Blood (126) | ↓ F/B (191) | ↑ Epithelial barrier (123) | ↓ MC activation (131) | ↓ Inflammatory cytokine and iNOS production in various immune models (129–131) | |||||||
| Glu | ↑ Blood and brain (126) | ↑ Epithelial barrier (124, 125) | ↓ Th2 cells (132, 133) | ↑ Treg cells and regulatory cytokine IL-10 (132, 133) | Neurotoxic at high levels (135) | |||||||
| Arg | - (126) | ↓ F/B (190) | ||||||||||
| Trp | ↓ Blood (126) | ↓ Intestinal inflammation (151, 152) | Essential for serotonin synthesis (149, 150) | Essential for serotonin synthesis (149, 150) | ||||||||
A selection of the complex effects of AAs on (from left to right) the microbiota composition, intestinal inflammation and intestinal barrier function, the immune system, mTOR activity and on cells in the brain. This table is limited to the effects that are relevant for ASD. The ↓ indicates a downregulation of the corresponding target by the specific amino acid, whereas the ↑ indicates an upregulation. Leu, leucine; Ile, isoleucine; Val, valine; His, histidine; Thr, threonine; Lys, lysine; Gly, glycine; Gln, glutamine; Glu, glutamate; Arg, arginine; Trp, tryptophan; MC, mast cell; EC, epithelial cell; CSF, cerebrospinal fluid; SCFA, short chain fatty acids; F/B, Firmicutes/Bacteroidetes ratio; PBMC, peripheral blood mononuclear cells; Ig, immunoglobulin; LPS, lipopolysaccharide; NO, nitric oxide; iNOS, inducible nitric oxide synthase; mΦ, macrophages; Th2, T helper 2 cells; Th17: T helper 17 cells; Treg, regulatory T cells.