Studies on immunogenic lipids from the gut microbiome

The gut microbiome’s composition influences human health both positively and negatively, and most of these influences involve regulating inflammatory immune responses. (1) For example, multiple studies, including in vivo human studies, have shown that Muciniphila akkermansia has positive effects on metabolism and response to cancer immunotherapy, but the underlying molecular mechanism for these responses remains unknown. Finding the answer to this and many similar questions is complicated because it requires deconvoluting the interaction of two complex systems: the gut microbiome and our immune systems. In collaboration with Ramnik Xavier’s laboratory (MGH, Broad, and Department of Genetics) we believe that we have found the answer: a small phospholipid making up part of the M. akkermansia’s cell membrane. Synthetic lipid recapitulates the effects of isolated lipid and of the intact bacteria. We plan to explore the structure-activity space to develop therapeutic agents that could be used as vaccine adjuvants, metabolic disease modifiers, and cancer chemotherapy enhancers.