To maintain a healthy symbiotic relationship with gut bacteria, the host immune system must tolerate bacterial molecules. A number of host mechanisms have been reported to mediate this tolerance; however, bacterial mediators of host tolerance are still mostly unknown. Bacterial lipopolysaccharide (LPS) is a potent activator of host innate immune signalling via Toll-like receptor 4 (TLR4) pathways; however, antagonistic forms of LPS have recently been reported. In a new study, total LPS was purified from the gut microbiota and its immunostimulatory potential was assessed. Total purified LPS had a significantly lower stimulatory effect compared with LPS purified from Escherichia coli, demonstrating that total LPS has a limited capacity to activate innate immunity. Using metagenomics, the authors delineated strain level contributions to the LPS pool and found that members of the Bacteroidales, which are dominant members of the gut microbiota, produce antagonistic forms of LPS and thereby drive immune tolerance of the entire community.