In a newly described murine model of BRAF-mutated colorectal cancer (CRC), we report the striking finding that addition of a single bacterium, enterotoxigenic Bacteroides fragilis (EBTF), to the complex microbiota in mice that combine the mutation of the common CRC tumor suppression gene, Apc, with the common V600E-activating mutation of BRAF, drives enhanced colon tumorigenesis but the resulting MSS tumors are now responsive to programmed cell death ligand-1 (PD-L1) blockade. In contrast, ETBF-induced MSS tumors in the setting of Apc mutation along are ICI non-responsive. We propose to dissect both tumor-cell intrinsic and immunologic mechanisms underlying the microbiota-linked switch to ICI responsiveness that could have profound significance for guiding immunotherapy of MSS CRC patients.