of molecules that shape or effect brain functions. These notably include things like neutral amino acids L-DOPA, tryptamine and -PEA. 4. Supplies and Methods 4.1. Mining of Human Expression Atlases Data mining analyses had been performed and repeated at the very least 3 times in between September 2020 and July 2021. We limited our survey of human expression atlases to important genes enabling the conversion of tyrosine, tryptophan and/or phenylalanine into dopamine and/or trace amines. We also incorporated in our search the sulfatases SULT1A1, SULT1A2 and SULT1A3, which support the conversion of dopamine into dopamine-sulfate, the key blood-circulating kind of dopamine [38,73]. Ultimately, we took into consideration the fact that L-DOPA is physiologically synthesized by gut microbiota [28,74] and is Brd site absorbed by intestinal enterocytes via particular influx transporters (SLC7A9 and SLC3A1) and efflux transporters (SLC16A10, SLC7A8 and SLC3A2) [75]. On this basis, the following genes of interest were hence retained for additional analyses:Dopa-decarboxylase (DDC): an enzyme enabling the synthesis of dopamine from LDOPA, the synthesis of tyramine from tyrosine [43], the synthesis of beta-phenylethy lamine (-PEA) from phenylalanine as well as the synthesis of tryptamine from tryptophane [18,76]; Cytochrome P450 family 2 subfamily D member six (CYP2D6): an enzyme Caspase 3 site allowing the synthesis of dopamine from tyramine [43]; Solute carrier family 7 member 9 (SLC7A9) and solute carrier family members 3 member 1 (SLC3A1): transporters allowing the cellular influx of L-DOPA [75]; Solute carrier family members six member ten (SLC16A10), solute carrier family members 7 member 8 (SLC7A8) and solute carrier loved ones 3 member two (SLC3A2): transporters allowing the cellular efflux of L-DOPA [75]; Sulfotransferase loved ones 1A member 1 (SULT1A1), sulfotransferase family 1A member two (SULT1A2), sulfotransferase family 1A member 3 (SULT1A3): enzymes allowing the sulfation of dopamine, top to the generation of dopamine 3-O-sulfate and dopamine 4-O-sulfate [38,73];Int. J. Mol. Sci. 2021, 22,11 ofMonoamine oxidase A (MAOA): an enzyme basically allowing the catabolism of dopamine and tyramine [77,78]; Monoamine oxidase B (MAOB): an enzyme permitting the catabolism of dopamine, tryptamine and -PEA [53,78,79].In parallel, precisely the same transcriptomic datasets had been mined to assess in human smaller intestine enterocytes the basal expression of ACE2 (angiotensin-converting enzyme 2) and SLC6A19 (solute carrier family members six member 19, the gene coding for the neutral amino acid transporter that physically interacts with ACE2). As a damaging handle, we also extracted data regarding the enterocytic expression of tyrosine hydroxylase (TH), a gene supporting the generation of L-DOPA from tyrosine and whose expression pattern is restricted to catecholaminergic cells with the adrenal glands and to dopaminergic neurons [80]. To explore in human tiny intestine enterocytes the steady state expression levels with the above-mentioned set of genes, we initially extracted benefits gathered within the genomics and proteomics database “Human Protein Atlas” (HPA) (proteinatlas.org/ (accessed on 24 September 2021)) [81]. In specific, we queried the HPA consensus dataset, which was obtained by compiling and normalizing the presently 3 largest mRNA expression atlases obtained from the analysis of regular human tissues and cells: the HPA dataset (proteinatlas.org/ (accessed on 24 September 2021)), the FANTOM5 dataset (fantom.gsc.riken.jp/5/ (accessed on 24 September 2021)) [82] along with the GTEx dataset