Gut microbes impact stroke severity

Here we show that gut microbiota directly impact host susceptibility for stroke, and adverse outcomes following stroke, through the dietary choline, gut microbiota, TMAO pathway. In initial gnotobiotic mouse stroke model studies, fecal microbial transplantation into germ-free recipient mice from low versus high TMAO-producing human donors was shown to transmit both capacity for TMAO generation and stroke severity. Next, employing independent murine stroke models with conventionally-reared mice, we showed that dietary supplementation with either choline or TMAO enhanced both cerebral infarct size and motor functional deficits. Finally, in additional gnotobiotic transplantation studies employing a synthetic microbial community lacking choline to trimethylamine (TMA) transforming activity plus/minus genetically engineered human commensals (wild-type versus delta cutC mutant), we show that harboring a functional gut microbial cutC gene is sufficient to transmit enhanced TMA(O) production, cerebral infarct size and functional deficits within a host. Collectively, these studies reveal that gut microbiota in general, and the TMAO pathway specifically, directly impacts host susceptibility for stroke and its adverse functional outcomes.