4D pharma showed that specific single bacterial strains from the human gut microbiota can serve as therapeutic inhibitors of the human enzyme histone deacetylase (HDAC), which is particularly relevant for disease areas involving host epigenetic aberrations.
According to the paper titled “Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid” published in PLOS ONE, the peer-reviewed open access scientific journal, overexpression of isoforms of HDAC has been implicated in a variety of diseases, including cancer, colitis, cardiovascular disease and neurodegeneration. HDAC inhibitors have a long history as therapeutic targets and the gut microbiota is known to have an influence on HDAC activity via microbial-derived metabolites. In this study, researchers used an in vitro approach to screen the 4D bacterial library to identify strains which inhibit different HDAC isoforms. One identified strain, MRx0029, was added to a model microbial consortium to assess its metabolic activity in interaction with a complex bacterial community. They found that MRx0029 successfully established in the consortium and enhanced the total and specific HDAC inhibitory function by increasing the capacity of the community to produce butyrate and valeric acid.
Dr. Alex Stevenson, 4D’s Chief Scientific Officer, said that the work shows that microbiome-derived live biotherapeutics can inhibit specific HDAC activity via previously unknown mechanisms. He said that this could lead to new live biotherapeutic therapies targeting this class of enzymes for conditions including cancer, neurodegenerative disorders and inflammatory pathologies. He also said that, in developing a model microbiome consortium, the ability of single-strain live biotherapeutics to induce community-wide functional changes in the microbiome and impact disease-relevant host signaling pathways was shown.