Gut Microbiota As Effectors Of Cell Physiology And As Potential Therapeutic Vectors

By Darryl Leja, NHGRI - http://www.genome.gov/dmd/img.cfm?node=Photos/Graphics&id=85320, Public Domain, https://commons.wikimedia.org/w/index.php?curid=29534265

It is known that microbiota, particularly gastrointestinal bacteria, can have a profound effect on human health.  This study (linked here) shows another mechanism by which this occurs – the bacteria can produce compounds that affect signaling pathways in human cells, potentially regulating metabolic hormones and glucose levels. Thus, bacteria can produce factors that mimic human equivalents, affecting human cell physiology, and thus influencing human health. The authors propose “microbiome-biosynthetic gene therapy” – leveraging this ability of microbes to have them produce factors that can promote therapeutic changes in the human system.  Abstract:

Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but 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 that they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiological role in humans. Our results suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-molecule therapeutic modality (microbiome-biosynthetic gene therapy).