Akkermansia muciniphila, a species of the human gut microbiome, has been robustly associated with positive systemic effects on host metabolism and obesity, favorable response to checkpoint blockade in cancer immunotherapy, and maintenance of homeostatic immunity. The Clardy lab at Harvard Medical School has identified a molecular mediator that recapitulates the desirable immunomodulatory effects associated with this important member of the human gut microbiota.

The research team isolated a naturally occurring diacyl phosphatidylethanolamine lipid from the cell membrane of Akkermansia muciniphila that selectively modulates human immune responses. Pre-treatment by the natural lipid and equipotent synthetic analogs was found to suppress pro-inflammatory cytokine release by TLR2-TLR1 and TLR4 agonists. These lipids are hypothesized to induce low-level stimulation of the TLR2–TLR1 signaling pathway to modulate the immunological tone of the host immune system by resetting the activation threshold to moderate strong pro-inflammatory signals and ignoring weak signals to restore homeostatic immunity.

These analogs have potential for therapeutic applications including T2DM, obesity, inflammatory bowel disease, and improving immunotherapy treatment for colorectal and breast cancer.

The research was published in Nature.