2017
DOI: 10.1038/nature23874
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Abstract: Summary Statement Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they en… Show more

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Cited by 353 publications
(273 citation statements)
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“…Although thousands of metabolites are commercially available, a limiting aspect of MAS can be the lack of commercially available reference materials for activity validation, particularly for lesser known or characterized metabolites. In those cases, the potential solutions available at present involve synthetic or isolation strategies, and for the most part, the former is the more common approach because large amounts of sample are rarely available to undertake isolation attempts 40 .…”
Section: Discussionmentioning
confidence: 99%
“…Although thousands of metabolites are commercially available, a limiting aspect of MAS can be the lack of commercially available reference materials for activity validation, particularly for lesser known or characterized metabolites. In those cases, the potential solutions available at present involve synthetic or isolation strategies, and for the most part, the former is the more common approach because large amounts of sample are rarely available to undertake isolation attempts 40 .…”
Section: Discussionmentioning
confidence: 99%
“…Orphan receptors may also require additional signalling partners that were absent from our experimental setups, such as other GPCRs or receptor activity-modifying proteins (Lorenzen et al, 2019;Wang et al, 2019). Alternatively, these receptors may not have peptide ligands or be constitutively active (Martin, Steurer, & Aronstam, 2015), or their activating molecules may be produced exogenously, as suggested for microbiome-derived ligands for GPR119 (Cohen et al, 2017). These are all potential areas for future investigation.…”
Section: Bbmentioning
confidence: 99%
“…Moreover, the production of aromatic acids by Clostridium sporogenes has been suggested to modulate host immunity . Furthermore, targeted screening of specific microbiota species and their metabolites with different protein families such as GPCRs have revealed new commensal bacteria and metabolite interactions . These exciting studies suggest specific microbiota species might generate unique metabolites to alter host immunity or infection, but the protein targets and mechanism(s) of action for these microbiota‐derived metabolites in host cells and/or microbes have not been fully characterized, thus could benefit from future studies with chemical reporters.…”
Section: Exploration Of Microbiota Mechanisms With Chemical Reportersmentioning
confidence: 99%