Therapeutic effectiveness of gut-associated methanogens in the prevention of atherosclerosis:

Most host-associated microbial communities studies focused on bacterial, fungal, or viral communities, but the archaeal component has often been neglected. Host–archaeome interactions have mostly been delineated from methanogenic archaea in the gastrointestinal tract, where they contribute to substantial methane production and are potentially also involved in disease-relevant processes. We aim to investigate the role of gut-associated methanogenic archaea to combat atherosclerosis and other trimethylamine-associated diseases. Trimethylamine (TMA) produced by gut microbiota from dietary ingredients is further oxidized into trimethylamine- oxide (TMAO) in the liver and contributes towards atherosclerosis and other clinical effects. Therefore, prevention of these diseases could rely on lowering the TMA level by human gut-associated TMA-utilizing methane-producing anaerobes ('archaebiotics') that convert TMA into non-reactive methane. We are working to elucidate the bioenergetics and oxidative stress response of archaebiotics. Further, we will employ these findings to encapsulate archaebiotics into nanoparticles to develop nanoarchaebiotics similar to nanoprobiotics for efficient delivery into the gut. Finally, we will determine the effect of nanoarchaebiotics on Apolipoprotein E knockout mice (a human atherosclerosis model). We will also look for other potential collaborators working on TMA-associated disease, including the human model, to understand the role of methanogens in combating cardiovascular-related disease.