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A putative binding site for a binding protein on rat intestinal epithelial cell membranes. Molecular structure of the toxin domain of heat-stable enterotoxin produced by a pathogenic strain of Escherichia coli. Production of ɑ-galactosylceramide by a prominent member of the human gut microbiota. Discovery of reactive microbiota-derived metabolites that inhibit host proteases. Bile salt biotransformations by human intestinal bacteria. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology. Specialized metabolites from the microbiome in health and disease. Small molecules from the human microbiota.
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Gut microbiota-generated metabolites in animal health and disease. Natural product discovery from the human microbiome. FAAs produced by Clostridia may serve as a mechanism to modulate their host by mimicking human signalling molecules. Lauroyl tryptamine is found to be an antagonist to the immunomodulatory receptor EBI2 against its native oxysterol ligand (0.98 μM half-maximal inhibitory concentration), is produced in culture by Eubacterium rectale and is present in human faecal samples. These molecules were screened against panels of human G-protein-coupled receptors to deduce their putative human targets. Using an in vitro assay, we tested their ability to incorporate 25 fatty acids and 53 amines known to be present in the human gut, from which the production of six FAAs was deduced (oleoyl dopamine, oleoyl tyramine, lauroyl tryptamine, oleoyl aminovaleric acid, α-linolenoyl phenylethylamine and caproyl tryptamine). These clusters were discovered to make FAAs by fusing exogenous fatty acids with amines. We identified a set of uncharacterized gene clusters in metagenomics data from the human gut microbiome. The molecules produced by human-associated microbes are difficult to identify because they may only be made in a local niche or they require a substrate sourced from the host, diet or other microbes. Human physiology is regulated by endogenous signalling compounds, including fatty acid amides (FAAs), chemical mimics of which are made by bacteria.