Distribution of bile acids and related transcripts/proteins. Distribution of observed bile acids as documented with the mass spectrometry reanalysis of data user interface in a) human and b) mouse. Briefly, sample information and metadata available in the public repositories were filtered for homo sapiens and mus/rattus. A search list adapted specifically for bile acids was used to subset a list of files where bile acids (only those that are curated in the GNPS spectral library) were detected. Total count of such files across different body regions as defined by the UBERONBodyPartName ontology in ReDU was calculated and described for humans and mice. For transcript locations, all matches discussed are to “bile” in the c) Human Protein Atlas23 and d) mouse gene expression database101. Black circles represent the number of bile acid-associated genes or gene products observed in respective body locations. Overlaid is the information about the bile acid receptor proteins, FXR, SXR (humans), PXR (mouse), BAAT, and TGR5. All panels are made using Biorender.com. Data and codes used for the reanalysis to create this figure are made available in the data availability section. It should be noted that inferences of differential distribution should not be inferred between organisms from this figure but rather as a documentation where transcripts, proteins, and bile acids have been detected. It is also an incomplete picture as many organs or biofluids have not been studied by transcriptomics, proteomics or metabolomics, let alone under all conditions that may alter the detection but gives an overview just how widely the bile acid metabolic and gene network is distributed throughout the body. BSH = bile salt hydrolase, BAAT = Bile acid-CoA:amino acid N-acyltransferase
Bile acids biosynthesized in the liver (termed primary bile acids) are stored in the gall bladder, where they are conjugated to taurine and glycine, and then released into the samll intestine after a meal for the digestion of fats and nutrients in the food. These primary bile acids can be modified by the gut microbiota to produce a diverse spectrum of bile acids, with modifications like dehydroxylation and oxidation on the steroid core or amidation with different amines and amino acids on the side chain. In this figure both the primary and secondary bile acids (only C24 bile acids) have been grouped as unconjugated (UNC; no conjuagtion on the side chain or the steroid core), glycine conjugated (GLY), taurine conjugated (TAU), amino acid conjugated (AA), methylated (MET), and oxidized (OXO; ketone groups on the carbon 3,7 or 12 in the steroid core). In accordance to previous literature, bile acids were detected in fecal, urine and blood matrices and also in lesser known body regions like skin, saliva and breast milk. Recently, bile acid producing capability has been demonstrated in the brain, and reanlysis of the public data for this figure highlighted the presence of unconjugated and taurine amidates of bile acids in mouse brain. In conclusion, the figure supports the wide distribution of bile acids through the human and mouse body which correlates to the presence of specific bile acid receptors and genes in different body parts as shown in figure 2c and 2d. The data used for generating this figure is publicly available in https://redu.ucsd.edu/
Proportion of bile acids in individual human subjects with data available in ReDU represented as normalized ion intensities across three biological matrices - a) urine b) blood, c) fecal. Each stacked bar represents a unique individual. Colors represent the seven bile acid groups - unconjugated, glycine conjugated, taurine conjugated, amino acid conjugated, oxidized, sulfated and tetrahydroxylated. The precursor ion intensities of the GNPS curated bile acids were extracted from the classical molecular network of all female and male samples across the three biological matrices as present in ReDU.
The plurality of bile acid distribution in three biological matrices, namely urine (3a), blood (3b) and feces (3c), across different human samples is discussed in this figure. Public data in ReDU was filtered for homo sapiens, followed by data acquired on Q-exactive mass spectrometer (QE) and the three different biological matrices using the file selection interface in ReDU (https://redu.ucsd.edu/metadataselection). Reanalysis with GNPS Classical molecular networking was launched with the filtered files and precursor ion intensities for GNPS curated bile acids were extratced and normalized using the total ion counts for each sample. The noramlized ion intensities are represented as stacked bar charts for the grouped bile acids. The colors represent the groups of uncojugated, glycine conjugated, taurine conjugated, amino acid conjugated, oxidixed steroid core, sulfation, and tetrahydroxylated bile acids.