Project description:Saccharibacteria (TM7) are obligate epibionts living on the surface of their host bacteria, and strongly correlated with dysbiotic microbiomes during periodontitis and other inflammatory diseases, suggesting they are putative pathogens. However, due to the recalcitrance of TM7 cultivation, no causal research has been conducted to investigate their role in inflammatory diseases. Here, we isolated multiple TM7 species on their host bacteria from periodontitis patients. These TM7 species reduced inflammation and consequential bone loss by modulating their host bacterial pathogenicity in mouse ligature-induced periodontitis model. Two host bacterial functions involved in collagen binding and utilization of eukaryotic sialic acid were identified as required for inducing bone loss and altered by TM7 association. This down-regulation of host bacterial pathogenicity by TM7 was shown for multiple TM7/host bacteria pairs, suggesting that, in contrast to their suspected pathogenic role, TM7 could protect mammalian hosts from inflammatory damage induced by their host bacteria.